REVIEW published: 09 December 2021 doi: 10.3389/fpls.2021.804468 The Arabidopsis Circadian Clock and Metabolic Energy: A Question of Time Luis Cervela-Cardona 1 , Benjamin Alary 1 and Paloma Mas 1,2* 1 Centre for Research in Agricultural Genomics, CSIC-IRTA-Universidad Autónoma de Barcelona (UAB)-UB, Barcelona, Spain, 2 Consejo Superior de Investigaciones Científicas, Barcelona, Spain A fundamental principle shared by all organisms is the metabolic conversion of nutrients into energy for cellular processes and structural building blocks. A highly precise spatiotemporal programming is required to couple metabolic capacity with energy allocation. Cellular metabolism is also able to adapt to the external time, and the mechanisms governing such an adaptation rely on the circadian clock. Virtually all photosensitive organisms have evolved a self-sustained timekeeping mechanism or circadian clock that anticipates and responds to the 24-h environmental changes that occur during the day and night cycle. This endogenous timing mechanism works in resonance with the environment to control growth, development, responses to stress, and also metabolism. Here, we briefly describe the prevalent role for the circadian clock Edited by: controlling the timing of mitochondrial activity and cellular energy in Arabidopsis thaliana. Wei Huang, South China Agricultural University, Evidence that metabolic signals can in turn feedback to the clock place the spotlight China onto the molecular mechanisms and components linking the circadian function with Reviewed by: metabolic homeostasis and energy. Norihito Nakamichi, Nagoya University, Japan Keywords: circadian clock, metabolism, mitochondria, ATP, Arabidopsis thaliana Meina Li, Guangzhou University, China *Correspondence: THE ARABIDOPSIS CIRCADIAN CLOCK: A BRIEF OVERVIEW Paloma Mas paloma.mas@cragenomica.es Multiple biological processes display a rhythmic oscillation with a period of approximately 24-h. The rhythms are sustained under constant environmental conditions indicating that are generated Specialty section: by a self-sustained timing mechanism or circadian clock. The core of the clock generates circadian This article was submitted to rhythms in output processes through the daily and seasonal synchronization, orchestrated largely Plant Physiology, by changes in light and temperature (Young and Kay, 2001). Many of the mechanistic insights of a section of the journal the circadian clock function in plants derive from studies in Arabidopsis thaliana (Sanchez and Frontiers in Plant Science Kay, 2016; McClung, 2019; Nakamichi, 2020). The number of clock components at the core of the Received: 29 October 2021 oscillator has been considerably expanded over the last years. Increasing evidence also highlight a Accepted: 17 November 2021 complex array of regulatory mechanisms that contribute to the rhythmic clock (Seo and Mas, 2014; Published: 09 December 2021 Mateos et al., 2018; Chen and Mas, 2019; Nakamichi, 2020). Citation: In broad outline, the current view of the circadian network includes a plethora of clock Cervela-Cardona L, Alary B and repressors that are expressed and function at specific times during the day and night. Clock Mas P (2021) The Arabidopsis Circadian Clock and Metabolic repressors include the morning-expressed MYB transcription factors CIRCADIAN CLOCK Energy: A Question of Time. ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY), as well as the members Front. Plant Sci. 12:804468. of the pseudo-response regulator (PRR) protein family PRR9 and PRR7 (Sanchez and Kay, 2016; doi: 10.3389/fpls.2021.804468 McClung, 2019; Nakamichi, 2020). Other members of the PRR family such as PRR5 and TIMING Frontiers in Plant Science | www.frontiersin.org 1 December 2021 | Volume 12 | Article 804468 Cervela-Cardona et al. Circadian Control of Metabolism OF CAB EXPRESSION1 (TOC1/PRR1, herein referred as without ATP synthesis, aiding the cell to cope with oxidative TOC1) are expressed later during the day or close to stress (Millar et al., 2011). dusk, respectively (Sanchez and Kay, 2016; McClung, 2019; In plants, mitochondrial and chloroplast activities are closely Nakamichi, 2020). The Evening complex (EC) composed of connected (Millar et al., 2011; Nunes-Nesi et al., 2011; Schertl ELF3 (EARLY FLOWERING 3, ELF4, and LUX/PCL1 (LUX and Braun, 2014). Both organelles behold electron transport ARRHYTHMO/PHYTOCLOCK1) functions in the evening to chains, which are responsible for the generation (chloroplasts) or repress the PRR morning genes (Sanchez and Kay, 2016; utilization (mitochondria) of reducing equivalents, translocation McClung, 2019; Nakamichi, 2020). These repressors configure of protons and the creation of the proton gradient as the a complicated regulatory network, which is complemented by boosting force for ATP synthesis. These mitochondrial and activating functions such as the rhythmic changes in chromatin chloroplastic metabolic reactions must be precisely coordinated marks (Chen and Mas, 2019) or clock components including in synchronization not only with the cellular status but also with LWD1 and 2 (LIGHT-REGULATED WD1 and 2) (Wu et al., the environmental conditions (Figure 1). Indeed, throughout 2008, 2016; Wang et al., 2011), or members of the RVE the day, plants assimilate carbon in form of soluble sugars (REVEILLE) protein family (Farinas and Mas, 2011; Rawat for immediate export and starch granules to be storage in et al., 2011; Hsu et al., 2013; Ma et al., 2018; Shalit-Kaneh the chloroplasts. Upon darkness, the stored starch is converted et al., 2018), which directly interact with the members of the into glucose and maltose that are then exported to the clock-related factors LNKs (NIGHT LIGHT-INDUCIBLE AND cytosol to supply the energetic demands in form of sucrose. CLOCK-REGULATED GENES) to recruit the transcriptional The generated sucrose and sucrose derivatives will be then machinery to activate clock gene expression (Ma et al., 2018). converted by glycolysis into pyruvate, which will be oxidized The importance of the circadian function in Arabidopsis through the TCA cycle. is reflected in the ample array of processes regulated by the Consistent with their primary function within the cell, both clock. The processes pervade nearly every aspect of development, organelles show high metabolic plasticity. During the day, the growth, or responses to biotic and abiotic stresses (Kinmonth- TCA cycle intermediates are required for nitrogen assimilation Schultz et al., 2013; Greenham and McClung, 2015; Sanchez and in chloroplasts such that the TCA cycle shifts into a non-cyclic Kay, 2016; Mora-García et al., 2017). The circadian clock also mode, affecting the formation of reducing equivalents (Sweetlove intersects with many relevant cellular processes and pathways et al., 2010). The organelles are also able to trigger alternative including among many others, aging (Kim et al., 2016), or the metabolic routes to keep a quasi-normal metabolic pace cell cycle (Fung-Uceda et al., 2018). Plants as other organisms, bypassing the predominant oxidative pathways. For instance, need to precisely control of the timing of energy production and under energy limitation conditions such as extended darkness, partitioning, enabling them to produce enough energy to cover short period or drought, plant mitochondria can completely for the cellular energetic demands. oxidize the Branched-Chain Amino Acids (BCAA) producing high amounts of ATP necessary for the plant to survive the metabolic stressful conditions (Pedrotti et al., 2018). CELLULAR ENERGY AND The bulk of ATP generation by plant mitochondria MITOCHONDRIAL ACTIVITY IN mostly occurs during the night. However, ATP produced ARABIDOPSIS by mitochondria at day time is important for other cellular processes such as sucrose biosynthesis and photorespiration Adenosine triphosphate (ATP) is a key energy carrier molecule (Bauwe et al., 2010). Photorespiration (also known as oxidative necessary for basic cellular functions in nearly all eukaryotic cells photosynthetic carbon cycle) relies on the uptake of molecular (Millar et al., 2011; Herst et al., 2017). Generation of ATP in oxygen concomitant with the release of carbon dioxide. mitochondria by oxidative phosphorylation relies on the transfer The gas exchange is similar to “dark” respiration, but the of electrons from reducing equivalents into oxygen (Braun, photorespiratory oxygen consumption occurs in chloroplasts, 2020). The reducing equivalents (such as nicotinamide adenine whereas the carbon dioxide is liberated in the mitochondria. dinucleotide, NADH, and flavin adenine dinucleotide, FADH2) The alternative NAD(P)H dehydrogenases contribute to the are formed through the tricarboxylic acid (TCA) cycle by the NADH re-oxidation capacities in mitochondria required in oxidation of organic compounds (Fernie et al., 2004). Coupling photorespiration (Bauwe et al., 2010). Also, the alternative the respiratory electron transfer chain with the electrochemical NAD(P)H dehydrogenases and the AOX, contribute to the proton gradient across the inner mitochondrial membrane is re-oxidization of the excess of reducing equivalents formed by used by the ATP synthase complex to phosphorylate adenosine the light reaction of photosynthesis (Braun, 2020). diphosphate (ADP), resulting in ATP to be used by the cell In this review, we provide a glimpse of some of the main (Ishizaki et al., 2006). Additional non-phosphorylating by-passes studies reporting the partitioning of cellular energy by the [non-energy conserving electron transfer from cytoplasmic and circadian clock in A. thaliana, with particular emphasis on matrix NAD(P)H to ubiquinone] are present in plants including mitochondrial function. Examples showing the feedback of alternative oxidase (AOX), NAD(P)H dehydrogenases, and metabolic signals controlling the clock are also briefly mentioned. uncoupling proteins (U) (Millar et al., 2011). When the canonical This review does not attempt to comprehensively describe every electron transfer chain is compromised, this alternative pathway study but rather to highlight the main findings connecting the allows the electron flux from NAD(P)H and succinate to oxygen circadian clock with the energetic balance in Arabidopsis. The Frontiers in Plant Science | www.frontiersin.org 2 December 2021 | Volume 12 | Article 804468 Cervela-Cardona et al. Circadian Control of Metabolism FIGURE 1 | Simplified view of the temporal partitioning by the circadian clock of central metabolism in photosynthetic cells. During the day, carbon is fixed through the photosynthetic reactions in the chloroplast and exported in the form of soluble sugars to the cytosol where it will be converted into pyruvate. In the dark, pyruvate feeds the mitochondrial respiration through the TCA cycle, and subsequently the mitochondrial mETC to generate ATP, which will be used for growth and development. cpETC, chloroplastic electron transport chain; CBB, Calvin-Benson-Bassham cycle; Pyru, Pyruvate; TCA, Tricarboxylic Acid Cycle; mETC, mitochondrial electron transport chain; ATP, adenosine triphosphate. readers are encouraged to consult excellent reviews focusing on the studies suggest a timely controlled adjustment of the the connection between the circadian clock and plant metabolism mitochondrial respiratory capacity and metabolism to meet the (e.g., Sanchez and Kay, 2016; Mora-García et al., 2017). energetic requirements over the diurnal cycle. An specific example of rhythmic oscillation includes the NAD- DEPENDENT MALIC ENZYME (NAD-ME) genes, which encode DIEL AND CIRCADIAN REGULATION OF members of the family of malic enzymes involved in metabolite MITOCHONDRIAL ACTIVITY flux through the TCA cycle (Tronconi et al., 2008). The NAD-ME gene expression and protein accumulation diurnally The circadian clock controls the rhythms of many different oscillate with peak abundance during the night. Metabolic metabolic pathways and organelles (Sanchez and Kay, 2016). analyses of NAD-ME loss-of-function mutants showed that Mitochondria are not an exception, and rhythmic trends these proteins might be important in the control of nocturnal of transcripts, proteins, metabolites, and ATP content have metabolism, including the regulation of TCA intermediates, been documented (Figure 2). For instance, Lee et al. (2010) glucosinolates, cell wall components, isoprenoids, fatty acids, and performed quantitative analysis of mitochondrial proteins plant immunity phytochemicals (Tronconi et al., 2008; Francisco over a diurnal cycle. The studies were complemented with et al., 2021). Together, the data suggest that NAD-ME may act as a analysis of enzyme activities and substrate-dependent respiratory key factor involved in the coordination of primary and secondary processes in isolated mitochondria (Lee et al., 2010). The metabolism in a time-dependent manner. The expression of authors identified about 55 mitochondrial protein spots that genes encoding other components of the TCA cycle for example dynamically changed over the diurnal cycle. The analyses also ISOCITRATE DEHYDROGENASE (Gibon et al., 2006) or showed the diurnal changes in mitochondrial activity driving FUMARASE 2 (Gibon et al., 2006; Cervela-Cardona et al., 2021) the TCA cycle and fluctuations associated with nitrogen and was also shown to be diurnally or circadianly-regulated. sulfur metabolism, and antioxidant defense. Additional studies Light is intimately connected with the circadian function. integrating transcripts, metabolite and enzyme activity profiling A recent study has focused on identifying the dynamic during diurnal cycles in Arabidopsis rosettes also reported that changes in protein-protein interactions within the TCA cycle, the diurnal changes in metabolism-related transcripts generate the mitochondrial glycine metabolism, and the mitochondria nearly stable metabolites, and suggested that metabolites might respiratory pathway in response to light (Rugen et al., 2021). modulate gene expression (Gibon et al., 2006). Altogether, By using a differential complexome profiling strategy, the Frontiers in Plant Science | www.frontiersin.org 3 December 2021 | Volume 12 | Article 804468 Cervela-Cardona et al. Circadian Control of Metabolism FIGURE 2 | Pervasive diel and circadian oscillation of mitochondrial activity. The circadian clock regulates the timing of mitochondrial activity. Connections of the clock with mitochondria include the regulation of gene expression, protein accumulation and function, protein-protein interaction and metabolite content. Please refer to the text for further details. authors assayed protein-protein interactions at two time points: chloroplastic Rubisco small subunit and Rubisco activase as before the end of the day and before the end of the night. well as the peroxisomal catalase, all components of the Comparative studies showed the formation of high molecular photorespiratory pathway (Pilgrim and McClung, 1993; Zhong mass protein complexes in the mitochondrial matrix during the et al., 1994; Zhong and McClung, 1996). Characterization of day, which differed from the ones observed at the end of the the Arabidopsis serine hydroxymethyltransferase (SHM) genes night. The mitochondrial complexes I and III, and the ATP encoding the mitochondrial matrix components involved in synthase complex also showed altered abundance between the photorespiration showed that they also exhibited circadian two conditions. The results thus pave the wave for a more oscillations that were in phase with those described for other comprehensive understanding of the mitochondria function photorespiratory genes (McClung et al., 2000). though the dynamic regulation of protein-protein interactions Consistent with the important role for the circadian clock during the day and night. coordinating the timing of the photorespiration, glycine, a As mentioned above, the alteration of mitochondria activity major substrate for mitochondrial photorespiration (Lernmark or energy-deprivation conditions trigger the use of alternative et al., 1991) is altered in TOC1 miss-expressing plants respiratory pathways such as the catabolism of Branched-Chain (Cervela-Cardona et al., 2021). Proper expression and function Amino Acids (BCAA) (Pedrotti et al., 2018). Assessment of of TOC1 might be thus important in the regulation of the rhythmic expression of BCAA genes with transcript co- photorespiration (Nunes-Nesi et al., 2010). As fumarate content expression analyses revealed positive correlations among BCAA is also affected by miss-expression of TOC1 (see below), it is catabolism genes and stress, development, diurnal/circadian, and possible that the changes in fumarate alter photorespiration light datasets (Peng et al., 2015). Transcript abundance was and nitrogen metabolism during the day, leading to a found to be reduced during the day and increased during the depletion (in TOC1-ox) or accumulation (in toc1-2) of glycine night. This oscillation was in agreement with a previous study (Cervela-Cardona et al., 2021). showing that free BCAA abundance rhythmically oscillates with Most of the studies in the laboratory are performed using a peak at the end of the day (Gibon et al., 2006). Some of the chambers with environmentally-controlled conditions. However, BCCA transcripts also oscillated under constant light conditions, these conditions usually differ or do not realistically recapitulate indicating a regulation by the circadian clock. Consistently, the fluctuations occurring under natural environments. the expression of BCAA genes was altered in TOC1 miss- Comparative analyses using plants grown under artificial light expressing plants (Cervela-Cardona et al., 2021), which suggest a and sunlight conditions showed that the metabolism of organic redirected proteolytic metabolism due to the altered energy status acids and amino acids was less robust than that of starch turnover in these plants. (Annunziata et al., 2017, 2018). These, and some other reports The clock is also linked with photorespiration, which involves (Nagano et al., 2012; Matsuzaki et al., 2015; Song et al., 2018) three different organelles: the mitochondrion, the chloroplast, highlight the necessity of growing plants under more natural and the peroxisome. Proper regulation of photorespiration field conditions. Additional studies incorporating coordinated requires a complex coordination of the expression of nuclear changes in irradiance and temperature also showed an altered genes encoding proteins targeted to the three different organelles. amplitude and a delayed peak phase of expression of circadian Early studies showed that the Arabidopsis circadian clock clock genes expressed around dawn such as LHY, CCA1, and controlled the rhythmic expression of genes encoding the PRR9 (Annunziata et al., 2017, 2018). The authors proposed Frontiers in Plant Science | www.frontiersin.org 4 December 2021 | Volume 12 | Article 804468 Cervela-Cardona et al. Circadian Control of Metabolism that the changes in phase might delay the clock activity until the importance of post-translational modifications and protein the temperature rises to allow metabolic activities such as degradation to fully understand the physiological and metabolic photosynthesis to commence. processes controlled by the clock (Graf et al., 2017). The use of mutants affecting clock genes expressed throughout the circadian cycle (dawn, morning, dusk, and evening) also COMPONENTS AND MECHANISMS uncovered the role of the circadian clock regulating starch CONNECTING THE CIRCADIAN CLOCK synthesis and the accumulation of organic acids and amino acids WITH METABOLIC ENERGY in the light (Flis et al., 2019). The results indicated that dawn components positively contributed to the accumulation of amino One key approach to examine the circadian regulation of acids, whereas the evening component likely activated starch metabolism relies on the use of relevant clock mutants and accumulation but repressed sucrose recycling. Furthermore, the over-expressing lines in order to examine changes in metabolism- authors proposed that the circadian clock was able to compensate related gene expression, protein abundance, enzyme activity, metabolism against the high load of carbon from photosynthesis. or metabolite content. Several studies have used this reverse Thus, a complex array of clock outputs regulate the turnover of genetic approach. One prime example includes the use of carbon and nitrogen reserves (Flis et al., 2019). the prr975 triple mutant (Fukushima et al., 2009). Metabolite A recent study has also provided a molecular mechanism profiling showed that the prr975 mutant plants displayed a connecting the circadian clock with mitochondria function significant increase of many intermediates of the TCA cycle. (Cervela-Cardona et al., 2021). The study showed that TOC1 Combining transcriptomics and metabolomics uncovered the is important for sustaining the rhythms of sugars, amino acids role of PRR9, PRR7, and PRR5 in the regulation of the and a number of TCA cycle intermediates. TOC1 also regulates biosynthetic pathways of chlorophyll, carotenoid, abscisic acid, the rhythms of ATP production by mitochondria. Consistently, and α-tocopherol (Fukushima et al., 2009). Thus, mitochondria miss-expression of TOC1 results in a variety of molecular and and chloroplast homeostasis are direct circadian clock outputs physiological phenotypes resembling energy-deprivation status. and proper expression and function of these PRR components is The regulation of metabolism by TOC1 relies on its binding to the important to sustain the metabolic homeostasis. promoter of the TCA-related gene FUMARASE 2 (FUM2), which Another example includes the clock component TIME FOR correlates with the repression of FUM2 expression at night, and COFFEE (TIC), which contributes to clock resetting at dawn with reduced fumarate accumulation (Figure 3). The results thus (Hall et al., 2003; Ding et al., 2007). Analyses with the loss provide a mechanistic explanation for the diurnal and circadian of function mutant showed major changes in the expression regulation of FUM2 expression and fumarate accumulation (Chia of genes related to various pathways including metabolism et al., 2000; Pracharoenwattana et al., 2010; Cervela-Cardona (Sanchez-Villarreal et al., 2013). Consistently, tic mutant plants et al., 2021). Altogether, the study suggests that TOC1 and its showed increased glutathione, and readjustments of amino acids control of FUMARASE 2 contribute to the regulation of energy and polyamine pools, which correlated with phenotypes such homeostasis during the day and night. as excess of starch, altered soluble carbohydrate abundance, Additional molecular connectors between mitochondria and hypersensitivity to oxidative stress and resistance to drought. the circadian clock include the TCP (TEOSINTE BRANCHED 1, Comparative analyses of transcriptomic and metabolomic data CYCLOIDEA, and PCF) family of transcriptions factors, which confirmed a role for TIC regulating plant metabolism (Sanchez- regulate plant growth and development (Nicolas and Cubas, Villarreal et al., 2013). Further studies also uncovered a genetic 2016). Promoter analyses identified site II regulatory elements interaction between TIC and AKIN10, a catalytic subunit of [TGGGC(C/T)] that contribute to the transcriptional activation the evolutionarily conserved key energy sensor sucrose non- or repression of genes encoding mitochondria-related proteins fermenting 1 (Snf1)-related kinase 1 (SnRK1) (Shin et al., 2017). (Giraud et al., 2010). TCP transcriptions factors not only bind to The study showed that inducible over-expression of AKIN10 the site II elements but also interact with core clock components lengthened the circadian period and delayed the phase of the such as LHY and PRR5. Therefore, the TCP proteins connect clock gene GIGANTEA (GI), and that this regulation required a the circadian clock with mitochondrial function through their functional TIC (Shin et al., 2017). binding to the site II elements to control gene expression and The analyses of two time points (end-of-day and end- organelle protein abundances (Giraud et al., 2010). of night) by RNA-sequencing and protein mass spectrometry with a battery of core clock mutants also revealed particular sets of mitochondrial-related genes and proteins miss-regulated METABOLIC FEEDBACK TO THE for each core clock component (Graf et al., 2017). The CIRCADIAN CLOCK comparative analyses also showed the lack of correlative changes in protein abundance and in the corresponding transcript in Metabolites and metabolic changes in turn feedback to regulate many instances. Transcripts and proteins with coordinated the diurnal and circadian oscillation of gene expression. For changes in abundance were enriched in carbohydrate- and cold- instance, nitrogen (N) is an important nutrient and nitric responsive genes, whereas genes encoding transcription factors, oxide (NO) is used as metabolic signal that regulates gene starch degradation enzymes, and protein kinases were found in expression in plants (Balotf et al., 2018). Gutiérrez et al. (2008) all circadian clock mutants examined. The authors highlighted identified glutamate (Glu) or glutamine (Gln) as regulators of Frontiers in Plant Science | www.frontiersin.org 5 December 2021 | Volume 12 | Article 804468 Cervela-Cardona et al. Circadian Control of Metabolism FIGURE 3 | A molecular mechanism connecting the circadian clock with cellular ATP. The expression of the TCA cycle related gene known as FUMARASE 2 (FUM2) oscillates with a peak phase during the day. Fumarate accumulation is important for growth and amino acid assimilation. TOC1 binds to the promoter of FUM2 to repress its expression at night. Consequently, the ATP/ADP ratio, a measure of energy homeostasis, is altered in TOC1 miss-expressing plants. White box: day; gray box: night; Green arrow: activation; red lines: repression. CCA1 expression. The authors also found that CCA1 in turn Sugar signals were also shown to entrain the clock through contributed to the N-assimilatory pathway, providing a novel the morning-expressed clock component PRR7 (Haydon et al., feedback mechanism by which N-assimilation functions as an 2013; Frank et al., 2018). Mathematical analyses and experimental input to the circadian clock, while in turn the clock regulates validation also identified the clock component GIGANTEA N-assimilation through CCA1 (Gutiérrez et al., 2008). These (GI) as an important sensor necessary for the full response results were consistent with previous studies showing that the of the circadian clock to sucrose (Dalchau et al., 2011). expression of two nitrate reductase genes, NIAI and NIA2 (Cheng A number of additional molecular components contributing to et al., 1988; Crawford et al., 1988) showed diurnal oscillations the adjustment of the circadian phase by sugars has been also with peak abundance occurring shortly after dawn (Cheng identified. Examples include the TREHALOSE-6-PHOSPHATE et al., 1991; Pilgrim and McClung, 1993). The oscillations were SYNTHASE1 (TPS1) and the sugar-sensing kinase SnRK1 that sustained under constant light and under constant darkness controls the transcription factor BASIC LEUCINE ZIPPER63, indicating that rhythms were controlled by the circadian clock. which in turn regulates PRR7 expression in response to sugars The oscillation of gene expression was functionally relevant, as (Frank et al., 2018). the circadian oscillations in NIA2 expression correlated well with Another factor required for the circadian clock to respond rhythms in nitrate reductase activity. to sucrose is SENSITIVE TO FREEZING 6 (SFR6) (Knight The use of the starchless phosphoglucomutase (pgm) mutant et al., 2008). The changes in amplitude and phase of clock- (Caspar et al., 1985) also uncovered that endogenous changes of related genes induced by sucrose were found to be reduced sugars regulated around half of the circadian-controlled genes in sfr6 mutant plants. Sucrose can also impact the circadian encoding putative transcription factors, and proteins involved in oscillator by increasing superoxide abundance (Román et al., the regulation of DNA, RNA, protein synthesis, and degradation 2021). Indeed, not only superoxide-regulated transcripts are (Blasing et al., 2005). The analyses suggested that low abundance regulated by the circadian clock, but also the regulation of TOC1 of sugars at the end of the night were responsible for the majority expression by sucrose in the evening requires superoxide. Thus, of the changes. Mathematical modeling also showed that the the authors provide evidence for a role for superoxide as part dynamic adjustments of the circadian clock to cellular sucrose of the sugar signaling pathway regulating the rhythms of clock modulated starch turnover, and thus, the circadian responses to gene expression. sucrose signals contribute to carbon homeostasis and improved A recent study has also reported a mechanism contributing growth (Seki et al., 2017). to the metabolic sugar input to the circadian clock Frontiers in Plant Science | www.frontiersin.org 6 December 2021 | Volume 12 | Article 804468 Cervela-Cardona et al. Circadian Control of Metabolism (Shor et al., 2017). The study showed that light not only time points of the plant life cycle. The need for a precise drives photosynthesis but also favors the phosphorylation and timely coordination of photosynthesis, respiration, and and degradation of the PHYTOCHROME INTERACTING photorespiration also raises the question about the role of FACTORS (PIFs), the negative regulators of the phytochrome the circadian clock controlling the temporal partitioning of signaling (Paik et al., 2017). However, the sugars produced the activity in mitochondria, chloroplasts, and peroxisomes by photosynthesis function in an opposite way to light i.e., in response to diurnal and seasonal changes. Identifying the activate PIFs abundance and the binding to the promoters of molecular components and regulatory mechanisms for such a CCA1 and LHY, to activate their expression. Thus, the study coordination lies as a challenge in front of us. Analyses of uncovers a role of PIFs regulating sucrose signals to the oscillator metabolic changes in response to external abiotic and biotic (Shor et al., 2017). threats, and the importance of the circadian clock contributing Early studies also showed that cyclic adenosine diphosphate to metabolic homeostasis under these conditions would be quite ribose (cADPR), driving the circadian oscillations of Ca2+ relevant, particularly in the context of the climate change. Studies release, was able to regulate the oscillator gene expression expanding the connection of the circadian clock and metabolism (Dodd et al., 2007). Another recent study has also shown that in crops of agronomical importance will also provide useful tools the target of rapamycin (TOR) kinase, a central regulator of for biotechnological manipulation of the circadian regulation growth, contributes to the glucose- and nicotinamide-dependent of metabolism in order to improve crop fitness, growth and regulation of circadian period by the clock (Zhang et al., 2019). productivity in resonance with the environment. The study proposes that nicotinamide regulates circadian period length by blocking the glucose-TOR energy signaling. Thus, the TOR kinase might function as an energy sensor for the timely AUTHOR CONTRIBUTIONS coordination of the circadian clockwork and plant growth. All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication. FINAL REMARKS Altogether, these studies convey the intimate relationship FUNDING between the Arabidopsis circadian clock, mitochondria activity, and the overall metabolic homeostasis of the cell. Neither The Mas Laboratory is funded with a research grant (PID2019- chloroplasts are just sites for photosynthesis and deposition of 106653GB-I00) from the MCIN/AEI/10.13039/501100011033, storage materials, nor mitochondria are just the powerhouse from the Ramon Areces Foundation and from the Generalitat of the cell. Chloroplasts aid on the compartmentalization of de Catalunya (AGAUR). PM laboratory also acknowledges the intermediary metabolism of cells. Purine and pyrimidine financial support from the CERCA Program/Generalitat de synthesis, most amino acid biosynthesis, and all the fatty acid Catalunya and by the Spanish Ministry of Economy and synthesis take place in chloroplasts. Mitochondria are also Competitiveness through the “Severo Ochoa Program for involved in subsidiary functions to the primary metabolism by Centers of Excellence in R&D” (CEX2019-000902-S). BA is participating in the photorespiration process, redox status and a recipient of a FPI fellowship (BES-2017-082261) funded by nitrogen assimilation. It would be thus interesting to identify MCIN/AEI/10.13039/501100011033 y FSE “El FSE invierte en tu the full contribution of the circadian clock in the regulation of futuro”. intermediary metabolism and the other processes and pathways controlled by the plant metabolic organelles. The range of energetic demands during different plant ACKNOWLEDGMENTS developmental stages and importantly, in different parts of the plant, calls for more specific studies focused on the We thank members of the Mas Laboratory for helpful discussion metabolic status in particular cells, tissues, or organs at different and suggestions. REFERENCES Bauwe, H., Hagemann, M., and Fernie, A. R. (2010). Photorespiration: players, partners and origin. Trends Plant Sci. 15, 330–336. doi: 10.1016/j.tplants.2010. Annunziata, M. G., Apelt, F., Carillo, P., Krause, U., Feil, R., Koehl, K., et al. 03.006 (2018). Response of Arabidopsis primary metabolism and circadian clock to low Blasing, O. E., Gibon, Y., Gunther, M., Hohne, M., Morcuende, R., Osuna, D., et al. night temperature in a natural light environment. J. Exp. Bot. 69, 4881–4895. (2005). Sugars and circadian regulation make major contributions to the global doi: 10.1093/jxb/ery276 regulation of diurnal gene expression in Arabidopsis. Plant Cell 17, 3257–3281. Annunziata, M. G., Apelt, F., Carillo, P., Krause, U., Feil, R., Mengin, V., et al. doi: 10.1105/tpc.105.035261 (2017). Getting back to nature: a reality check for experiments in controlled Braun, H. P. (2020). The Oxidative Phosphorylation system of the mitochondria in environments. J. Exp. Bot. 68, 4463–4477. doi: 10.1093/jxb/erx220 plants. Mitochondrion 53, 66–75. doi: 10.1016/j.mito.2020.04.007 Balotf, S., Islam, S., Kavoosi, G., Kholdebarin, B., Juhasz, A., and Ma, W. (2018). Caspar, T., Huber, S. C., and Somerville, C. (1985). Alterations in growth, How exogenous nitric oxide regulates nitrogen assimilation in wheat seedlings photosynthesis, and respiration in a starchless mutant of Arabidopsis thaliana under different nitrogen sources and levels. PLoS One 13:e0190269. doi: 10. (L.) Deficient in chloroplast phosphoglucomutase activity. Plant Physiol. 79, 1371/journal.pone.0190269 11–17. doi: 10.1104/pp.79.1.11 Frontiers in Plant Science | www.frontiersin.org 7 December 2021 | Volume 12 | Article 804468 Cervela-Cardona et al. Circadian Control of Metabolism Cervela-Cardona, L., Yoshida, T., Zhang, Y., Okada, M., Fernie, A., and Mas, P. Greenham, K., and McClung, C. R. (2015). Integrating circadian dynamics with (2021). Circadian control of metabolism by the clock component TOC1. Front. physiological processes in plants. Nat. Rev. Genet. 16, 598–610. doi: 10.1038/ Plant Sci. 12:1126. doi: 10.3389/fpls.2021.683516 nrg3976 Chen, Z. J., and Mas, P. (2019). Interactive roles of chromatin regulation and Gutiérrez, R. A., Stokes, T. L., Thum, K., Xu, X., Obertello, M., Katari, M. S., circadian clock function in plants. Genome Biol. 20:62. doi: 10.1186/s13059- et al. (2008). Systems approach identifies an organic nitrogen-responsive gene 019-1672-9 network that is regulated by the master clock control gene CCA1. Proc. Natl. Cheng, C. L., Acedo, G. N., Dewdney, J., Goodman, H. M., and Conkling, M. A. Acad. Sci. U.S.A. 105, 4939–4944. doi: 10.1073/pnas.0800211105 (1991). Differential expression of the two arabidopsis nitrate reductase genes. Hall, A., Bastow, R. M., Davis, S. J., Hanano, S., McWatters, H. G., Hibberd, V., Plant Physiol. 96, 275–279. doi: 10.1104/pp.96.1.275 et al. (2003). The time for coffee gene maintains the amplitude and timing of Cheng, C. L., Dewdney, J., Nam, H. G., den Boer, B. G., and Goodman, H. M. arabidopsis circadian clocks. Plant Cell 15, 2719–2729. doi: 10.1105/tpc.013730 (1988). A new locus (NIA 1) in Arabidopsis thaliana encoding nitrate reductase. Haydon, M. J., Mielczarek, O., Robertson, F. C., Hubbard, K. E., and Webb, A. A. R. EMBO J. 7, 3309–3314. doi: 10.1002/j.1460-2075.1988.tb03201.x (2013). Photosynthetic entrainment of the Arabidopsis thaliana circadian clock. Chia, D. W., Yoder, T. J., Reiter, W. D., and Gibson, S. I. (2000). Fumaric acid: an Nature 502, 689–692. doi: 10.1038/nature12603 overlooked form of fixed carbon in Arabidopsis and other plant species. Planta Herst, P. M., Rowe, M. R., Carson, G. M., and Berridge, M. V. (2017). Functional 211, 743–751. doi: 10.1007/s004250000345 mitochondria in health and disease. Front. Endocrinol. 8:296. doi: 10.3389/ Crawford, N. M., Smith, M., Bellissimo, D., and Davis, R. W. (1988). Sequence fendo.2017.00296 and nitrate regulation of the Arabidopsis thaliana mRNA encoding nitrate Hsu, P. Y., Devisetty, U. K., and Harmer, S. L. (2013). Accurate timekeeping is reductase, a metalloflavoprotein with three functional domains. Proc. Natl. controlled by a cycling activator in Arabidopsis. Elife 2:e00473. doi: 10.7554/ Acad. Sci. U. S. A. 85, 5006–5010. doi: 10.1073/pnas.85.14.5006 eLife.00473 Dalchau, N., Baek, S. J., Briggs, H. M., Robertson, F. C., Dodd, A. N., Gardner, Ishizaki, K., Schauer, N., Larson, T. R., Graham, I. A., Fernie, A. R., and Leaver, C. J. M. J., et al. (2011). The circadian oscillator gene GIGANTEA mediates a long- (2006). The mitochondrial electron transfer flavoprotein complex is essential term response of the Arabidopsis thaliana circadian clock to sucrose. Proc. Natl. for survival of Arabidopsis in extended darkness. Plant J. 47, 751–760. doi: Acad. Sci. U.S.A. 108, 5104–5109. doi: 10.1073/pnas.1015452108 10.1111/j.1365-313X.2006.02826.x Ding, Z., Millar, A. J., Davis, A. M., and Davis, S. J. (2007). Time for coffee encodes Kim, H., Kim, Y., Yeom, M., Lim, J., and Nam, H. G. (2016). Age-associated a nuclear regulator in the Arabidopsis thaliana circadian clock. Plant Cell Online circadian period changes in Arabidopsis leaves. J. Exp. Bot. 67, 2665–2673. 19, 1522–1536. doi: 10.1105/tpc.106.047241 doi: 10.1093/jxb/erw097 Dodd, A. N., Gardner, M. J., Hotta, C. T., Hubbard, K. E., Dalchau, N., Love, J., et al. Kinmonth-Schultz, H. A., Golembeski, G. S., and Imaizumi, T. (2013). Circadian (2007). The Arabidopsis circadian clock incorporates a cADPR-based feedback clock-regulated physiological outputs: dynamic responses in nature. Semin. Cell loop. Science 318, 1789–1792. doi: 10.1126/science.1146757 Dev. Biol. 24, 407–413. doi: 10.1016/j.semcdb.2013.02.006 Farinas, B., and Mas, P. (2011). Functional implication of the MYB transcription Knight, H., Thomson, A. J. W., and McWatters, H. G. (2008). Sensitive to freezing6 factor RVE8/LCL5 in the circadian control of histone acetylation. Plant J. 66, integrates cellular and environmental inputs to the plant circadian clock. Plant 318–329. doi: 10.1111/j.1365-313X.2011.04484.x Physiol. 148, 293–303. doi: 10.1104/pp.108.123901 Fernie, A. R., Carrari, F., and Sweetlove, L. J. (2004). Respiratory metabolism: Lee, C. P., Eubel, H., and Millar, A. H. (2010). Diurnal changes in mitochondrial glycolysis, the TCA cycle and mitochondrial electron transport. Curr. Opin. function reveal daily optimization of light and dark respiratory metabolism Plant Biol. 7, 254–261. doi: 10.1016/j.pbi.2004.03.007 in Arabidopsis. Mol. Cell. Proteomics 9, 2125–2139. doi: 10.1074/mcp.M110. Flis, A., Mengin, V., Ivakov, A. A., Mugford, S. T., Hubberten, H. M., Encke, 001214 B., et al. (2019). Multiple circadian clock outputs regulate diel turnover of Lernmark, U., Henricson, D., Wigge, B., and Gardeström, P. (1991). Glycine carbon and nitrogen reserves. Plant Cell Environ. 42, 549–573. doi: 10.1111/pce. oxidation in mitochondria isolated from light grown and etiolated plant tissue. 13440 Physiol. Plant. 82, 339–344. doi: 10.1111/j.1399-3054.1991.tb02915.x Francisco, M., Kliebenstein, D. J., Rodríguez, V. M., Soengas, P., Abilleira, R., Ma, Y., Gil, S., Grasser, K. D., and Mas, P. (2018). Targeted recruitment of the basal and Cartea, M. E. (2021). Fine mapping identifies NAD-ME1 as a candidate transcriptional machinery by LNK clock components controls the circadian underlying a major locus controlling temporal variation in primary and rhythms of nascent RNAs in arabidopsis. Plant Cell 30, 907–924. doi: 10.1105/ specialized metabolism in Arabidopsis. Plant J. 106, 454–467. doi: 10.1111/tpj. tpc.18.00052 15178 Mateos, J. L., de Leone, M. J., Torchio, J., Reichel, M., and Staiger, D. (2018). Beyond Frank, A., Matiolli, C. C., Viana, A. J. C., Hearn, T. J., Kusakina, J., Belbin, F. E., transcription: fine-tuning of circadian timekeeping by post-transcriptional et al. (2018). Circadian entrainment in Arabidopsis by the sugar-responsive regulation. Genes 9:616. doi: 10.3390/genes9120616 transcription factor bZIP63. Curr. Biol. 28, 2597.e6–2606.e6. doi: 10.1016/j.cub. Matsuzaki, J., Kawahar, Y., and Izawa, T. (2015). Punctual transcriptional 2018.05.092 regulation by the rice circadian clock under fluctuating field conditions. Plant Fukushima, A., Kusano, M., Nakamichi, N., Kobayashi, M., Hayashi, N., Cell 27, 633–648. doi: 10.1105/tpc.114.135582 Sakakibara, H., et al. (2009). Impact of clock-associated Arabidopsis McClung, C. R. (2019). The plant circadian oscillator. Biology 8:14. doi: 10.3390/ pseudoresponse regulators in metabolic coordination. Proc. Natl. Acad. Sci. biology8010014 U. S. A. 106, 7251–7256. doi: 10.1073/pnas.0900952106 McClung, C. R., Hsu, M., Painter, J. E., Gagne, J. M., Karlsberg, S. D., and Fung-Uceda, J., Lee, K., Seo, P. J., Polyn, S., De Veylder, L., and Mas, P. (2018). The Salomé, P. A. (2000). Integrated Temporal Regulation of the Photorespiratory circadian clock sets the time of DNA replication licensing to regulate growth in Pathway. Circadian Regulation of Two Arabidopsis Genes Encoding Serine arabidopsis. Dev. Cell 45, 101.e4–113.e4. doi: 10.1016/j.devcel.2018.02.022 Hydroxymethyltransferase. Plant Physiol. 123, 381–392. doi: 10.1104/pp.123.1. Gibon, Y., Usadel, B., Blaesing, O., Kamlage, B., Hoehne, M., Trethewey, R., et al. 381 (2006). Integration of metabolite with transcript and enzyme activity profiling Millar, A. H., Whelan, J., Soole, K. L., and Day, D. A. (2011). Organization and during diurnal cycles in Arabidopsis rosettes. Genome Biol. 7:R76. doi: 10.1186/ Regulation of Mitochondrial Respiration in Plants. Annu. Rev. Plant Biol. 62, gb-2006-7-8-R76 79–104. doi: 10.1146/annurev-arplant-042110-103857 Giraud, E., Ng, S., Carrie, C., Duncan, O., Low, J., Lee, C. P., et al. (2010). Mora-García, S., de Leone, M. J., and Yanovsky, M. (2017). Time to grow: circadian TCP transcription factors link the regulation of genes encoding mitochondrial regulation of growth and metabolism in photosynthetic organisms. Curr. Opin. proteins with the circadian clock in Arabidopsis thaliana. Plant Cell 22, 3921– Plant Biol. 35, 84–90. doi: 10.1016/j.pbi.2016.11.009 3934. doi: 10.1105/tpc.110.074518 Nagano, A. J., Sato, Y., Mihara, M., Antonio, B. A., Motoyama, R., Itoh, H., Graf, A., Coman, D., Uhrig, R., Walsh, S., Flis, A., Stitt, M., et al. (2017). Parallel et al. (2012). Deciphering and prediction of transcriptome dynamics under analysis of Arabidopsis circadian clock mutants reveals different scales of fluctuating field conditions. Cell 151, 1358–1369. doi: 10.1016/j.cell.2012.10.048 transcriptome and proteome regulation. Open Biol. 7:160333. doi: 10.1098/ Nakamichi, N. (2020). The transcriptional network in the arabidopsis circadian RSOB.160333 clock system. Genes 11, 1–13. doi: 10.3390/genes11111284 Frontiers in Plant Science | www.frontiersin.org 8 December 2021 | Volume 12 | Article 804468 Cervela-Cardona et al. Circadian Control of Metabolism Nicolas, M., and Cubas, P. (2016). TCP factors: new kids on the signaling block. across environmental conditions. Proc. Natl. Acad. Sci. U.S.A 115, 7147–7152. Curr. Opin. Plant Biol. 33, 33–41. doi: 10.1016/j.pbi.2016.05.006 doi: 10.1073/pnas.1805524115 Nunes-Nesi, A., Araújo, W. L., and Fernie, A. R. (2011). Targeting mitochondrial Shin, J., Sánchez-Villarreal, A., Davis, A. M., Du, S., Berendzen, K. W., Koncz, metabolism and machinery as a means to enhance photosynthesis. Plant C., et al. (2017). The metabolic sensor AKIN10 modulates the Arabidopsis Physiol. 155, 101–107. doi: 10.1104/pp.110.163816 circadian clock in a light-dependent manner. Plant. Cell Environ. 40, 997–1008. Nunes-Nesi, A., Fernie, A. R., and Stitt, M. (2010). Metabolic and signaling aspects doi: 10.1111/pce.12903 underpinning the regulation of plant carbon nitrogen interactions. Mol. Plant Shor, E., Paik, I., Kangisser, S., Green, R., and Huq, E. (2017). PHYTOCHROME 3, 973–996. doi: 10.1093/mp/ssq049 INTERACTING FACTORS mediate metabolic control of the circadian system Paik, I., Kathare, P. K., Kim, J. Il, and Huq, E. (2017). Expanding Roles of PIFs in Arabidopsis. New Phytol. 215, 217–228. doi: 10.1111/nph.14579 in Signal Integration from Multiple Processes. Mol. Plant 10, 1035–1046. doi: Song, Y. H., Kubota, A., Kwon, M. S., Covington, M. F., Lee, N., Taagen, E. R., 10.1016/j.molp.2017.07.002 et al. (2018). Molecular basis of flowering under natural long-day conditions in Pedrotti, L., Weiste, C., Nägele, T., Wolf, E., Lorenzin, F., Dietrich, K., et al. (2018). Arabidopsis. Nat. Plants 4, 824–835. doi: 10.1038/s41477-018-0253-3 Snf1-related kinase1-Controlled C/S1-bZIP Signaling Activates Alternative Sweetlove, L. J., Beard, K. F. M., Nunes-Nesi, A., Fernie, A. R., and Ratcliffe, R. G. Mitochondrial Metabolic Pathways to Ensure Plant Survival in Extended (2010). Not just a circle: flux modes in the plant TCA cycle. Trends Plant Sci. 15, Darkness. Plant Cell 30, 495–509. doi: 10.1105/tpc.17.00414 462–470. doi: 10.1016/j.tplants.2010.05.006 Peng, C., Uygun, S., Shiu, S. H., and Last, R. L. (2015). The impact Tronconi, M. A., Fahnenstich, H., Gerrard Weehler, M. C., Andreo, C. S., Flügge, of the branched-chain ketoacid dehydrogenase complex on amino acid U. I., Drincovich, M. F., et al. (2008). Arabidopsis NAD-malic enzyme functions homeostasis in Arabidopsis. Plant Physiol. 169, 1807–1820. doi: 10.1104/pp.15. as a homodimer and heterodimer and has a major impact on nocturnal 00461 metabolism. Plant Physiol. 146, 1540–1552. doi: 10.1104/PP.107.114975 Pilgrim, M. L., and McClung, C. R. (1993). Differential involvement of the circadian Wang, Y., Wu, J.-F., Nakamichi, N., Sakakibara, H., Nam, H.-G., and clock in the expression of genes required for ribulose-1,5-bisphosphate Wu, S.-H. (2011). LIGHT-REGULATED WD1 and PSEUDO-RESPONSE carboxylase/oxygenase synthesis, assembly, and activation in Arabidopsis REGULATOR9 Form a Positive Feedback Regulatory Loop in the Arabidopsis thaliana. Plant Physiol. 103, 553–564. doi: 10.1104/pp.103.2.553 Circadian Clock. Plant Cell Online 23, 486–498. doi: 10.1105/tpc.110.081661 Pracharoenwattana, I., Zhou, W., Keech, O., Francisco, P. B., Udomchalothorn, Wu, J. F., Tsai, H. L., Joanito, I., Wu, Y. C., Chang, C. W., Li, Y. H., et al. (2016). T., Tschoep, H., et al. (2010). Arabidopsis has a cytosolic fumarase required for LWD-TCP complex activates the morning gene CCA1 in Arabidopsis. Nat. the massive allocation of photosynthate into fumaric acid and for rapid plant Commun. 7:13181. doi: 10.1038/ncomms13181 growth on high nitrogen. Plant J. 62, 785–795. doi: 10.1111/j.1365-313X.2010. Wu, J. F., Wang, Y., and Wu, S. H. (2008). Two new clock proteins, LWD1 04189.x and LWD2, regulate arabidopsis photoperiodic flowering. Plant Physiol. 148, Rawat, R., Takahashi, N., Hsu, P. Y., Jones, M. A., Schwartz, J., Salemi, M. R., et al. 948–959. doi: 10.1104/pp.108.124917 (2011). REVEILLE8 and PSEUDO-REPONSE REGULATOR5 form a negative Young, M. W., and Kay, S. A. (2001). Time zones: a comparative genetics of feedback loop within the arabidopsis circadian clock. PLoS Genet. 7:e1001350. circadian clocks. Nat. Rev. Gen. 2, 702–715. doi: 10.1038/35088576 doi: 10.1371/journal.pgen.1001350 Zhang, N., Meng, Y., Li, X., Zhou, Y., Ma, L., Fu, L., et al. (2019). Metabolite- Román, Á, Li, X., Deng, D., Davey, J. W., James, S., Graham, I. A., et al. (2021). mediated TOR signaling regulates the circadian clock in Arabidopsis. Proc. Natl. Superoxide is promoted by sucrose and affects amplitude of circadian rhythms Acad. Sci. U. S. A. 116, 25395–25397. doi: 10.1073/pnas.1913095116 in the evening. Proc. Natl. Acad. Sci. U. S. A. 118:e2020646118. doi: 10.1073/ Zhong, H. H., and McClung, C. R. (1996). The circadian clock gates expression of pnas.2020646118 twoArabidopsis catalase genes to distinct and opposite circadian phases. Mol. Rugen, N., Schaarschmidt, F., Eirich, J., Finkemeier, I., Braun, H. P., and Eubel, H. Gen. Genet. 251, 196–203. doi: 10.1007/bf02172918 (2021). Protein interaction patterns in Arabidopsis thaliana leaf mitochondria Zhong, H. H., Young, J. C., Pease, E. A., Hangarter, R. P., and McClung, C. R. change in dependence to light. Biochim. Biophys. Acta Bioenerg. 1862:148443. (1994). Interactions between light and the circadian clock in the regulation of doi: 10.1016/j.bbabio.2021.148443 CAT2 expression in Arabidopsis. Plant Physiol. 104, 889–898. doi: 10.1104/pp. Sanchez, S. E., and Kay, S. A. (2016). The plant circadian clock: from a simple 104.3.889 timekeeper to a complex developmental manager. Cold Spring Harb. Perspect. Biol. 8:a027748. doi: 10.1101/cshperspect.a027748 Conflict of Interest: The authors declare that the research was conducted in the Sanchez-Villarreal, A., Shin, J., Bujdoso, N., Obata, T., Neumann, U., Du, S.-X., absence of any commercial or financial relationships that could be construed as a et al. (2013). TIME FOR COFFEE is an essential component in the maintenance potential conflict of interest. of metabolic homeostasis in Arabidopsis thaliana. Plant J. 76, 188–200. doi: 10.1111/tpj.12292 Publisher’s Note: All claims expressed in this article are solely those of the authors Schertl, P., and Braun, H. P. (2014). Respiratory electron transfer pathways in plant and do not necessarily represent those of their affiliated organizations, or those of mitochondria. Front. Plant Sci. 5:163. doi: 10.3389/fpls.2014.00163 the publisher, the editors and the reviewers. Any product that may be evaluated in Seki, M., Ohara, T., Hearn, T. J., Frank, A., da Silva, V. C. H., Caldana, C., et al. this article, or claim that may be made by its manufacturer, is not guaranteed or (2017). Adjustment of the Arabidopsis circadian oscillator by sugar signalling endorsed by the publisher. dictates the regulation of starch metabolism. Sci. Rep. 7:8305. doi: 10.1038/ s41598-017-08325-y Copyright © 2021 Cervela-Cardona, Alary and Mas. This is an open-access article Seo, P. J., and Mas, P. (2014). Multiple layers of posttranslational regulation refine distributed under the terms of the Creative Commons Attribution License (CC BY). circadian clock activity in Arabidopsis. Plant Cell 26, 79–87. doi: 10.1105/tpc. The use, distribution or reproduction in other forums is permitted, provided the 113.119842 original author(s) and the copyright owner(s) are credited and that the original Shalit-Kaneh, A., Kumimoto, R. W., Filkov, V., and Harmer, S. L. (2018). Multiple publication in this journal is cited, in accordance with accepted academic practice. No feedback loops of the Arabidopsis circadian clock provide rhythmic robustness use, distribution or reproduction is permitted which does not comply with these terms. Frontiers in Plant Science | www.frontiersin.org 9 December 2021 | Volume 12 | Article 804468