Web of Science: 5 citations, Scopus: 5 citations, Google Scholar: citations,
Grp78 overexpression triggers PINK1-IP3R-mediated neuroprotective mitophagy
Leiva-Rodríguez, Tatiana (Universitat Autònoma de Barcelona. Institut de Neurociències)
Romeo-Guitart, David (Universitat Autònoma de Barcelona. Institut de Neurociències)
Herrando-Grabulosa, Mireia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Muñoz-Guardiola, Pau (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Polo, Miriam (Hospital Universitari Doctor Peset (València))
Bañuls, Celia (Hospital Universitari Doctor Peset (València))
Petegnief, Valerie (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Bosch i Merino, Assumpció (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Lizcano de Vega, José Miguel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Apostolova, Nadezda (Universitat de València. Departament de Farmacologia)
Forés Vineta, Joaquim (Hospital Clínic i Provincial de Barcelona)
Casas Louzao, Caty (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date: 2021
Abstract: An experimental model of spinal root avulsion (RA) is useful to study causal molecular programs that drive retrograde neurodegeneration after neuron-target disconnection. This neurode-generative process shares common characteristics with neuronal disease-related processes such as the presence of endoplasmic reticulum (ER) stress and autophagy flux blockage. We previously found that the overexpression of GRP78 promoted motoneuronal neuroprotection after RA. After that, we aimed to unravel the underlying mechanism by carrying out a comparative unbiased proteomic analysis and pharmacological and genetic interventions. Unexpectedly, mitochondrial factors turned out to be most altered when GRP78 was overexpressed, and the abundance of engulfed mitochondria, a hallmark of mitophagy, was also observed by electronic microscopy in RA-injured motoneurons after GRP78 overexpression. In addition, GRP78 overexpression increased LC3-mitochondria tag-ging, promoted PINK1 translocation, mitophagy induction, and recovered mitochondrial function in ER-stressed cells. Lastly, we found that GRP78-promoted pro-survival mitophagy was mediated by PINK1 and IP3R in our in vitro model of motoneuronal death. This data indicates a novel relationship between the GRP78 chaperone and mitophagy, opening novel therapeutical options for drug design to achieve neuroprotection.
Grants: Ministerio de Economía y Competitividad SAF 2014-59701
Instituto de Salud Carlos III CP19/00077
Note: Altres ajuts: Marató de TV3 (201607.10)
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Subject: GRP78/BiP ; Mitophagy ; Motoneurons ; Neurodegeneration ; Neuroprotection
Published in: Biomedicines, Vol. 9 Núm. 8 (august 2021) , p. 1039, ISSN 2227-9059

DOI: 10.3390/biomedicines9081039
PMID: 34440243


20 p, 5.8 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2022-01-19, last modified 2022-07-16



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