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Article (Scientific journals)
PINK1 and BECN1 relocalize at mitochondria-associated membranes during mitophagy and promote ER-mitochondria tethering and autophagosome formation.
Gelmetti, Vania; De Rosa, Priscilla; Torosantucci, Liliana et al.
2017In Autophagy, 13 (4), p. 654-669
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Keywords :
Autophagosomes/metabolism; Beclin-1/metabolism; Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology; Cell Compartmentation/drug effects; Cell Line, Tumor; Down-Regulation; Endoplasmic Reticulum/metabolism; Humans; Mitochondria/metabolism; Mitochondrial Membranes/metabolism; Mitophagy; Protein Kinases/metabolism; BECN1; CCCP; PARK2; PINK1; Parkinson disease; autophagosome formation; endoplasmic reticulum-mitochondria tethering; mitochondria-associated membranes; omegasome
Abstract :
[en] Mitophagy is a highly specialized process to remove dysfunctional or superfluous mitochondria through the macroautophagy/autophagy pathway, aimed at protecting cells from the damage of disordered mitochondrial metabolism and apoptosis induction. PINK1, a neuroprotective protein mutated in autosomal recessive Parkinson disease, has been implicated in the activation of mitophagy by selectively accumulating on depolarized mitochondria, and promoting PARK2/Parkin translocation to them. While these steps have been characterized in depth, less is known about the process and site of autophagosome formation upon mitophagic stimuli. A previous study reported that, in starvation-induced autophagy, the proautophagic protein BECN1/Beclin1 (which we previously showed to interact with PINK1) relocalizes at specific regions of contact between the endoplasmic reticulum (ER) and mitochondria called mitochondria-associated membranes (MAM), from which the autophagosome originates. Here we show that, following mitophagic stimuli, autophagosomes also form at MAM; moreover, endogenous PINK1 and BECN1 were both found to relocalize at MAM, where they promoted the enhancement of ER-mitochondria contact sites and the formation of omegasomes, that represent autophagosome precursors. PARK2 was also enhanced at MAM following mitophagy induction. However, PINK1 silencing impaired BECN1 enrichment at MAM independently of PARK2, suggesting a novel role for PINK1 in regulating mitophagy. MAM have been recently implicated in many key cellular events. In this light, the observed prevalent localization of PINK1 at MAM may well explain other neuroprotective activities of this protein, such as modulation of mitochondrial calcium levels, mitochondrial dynamics, and apoptosis.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Gelmetti, Vania
De Rosa, Priscilla
Torosantucci, Liliana
Marini, Elettra Sara
Romagnoli, Alessandra
Di Rienzo, Martina
Arena, Giuseppe ;  IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université Montpellier, Institutrégional du Cancer Montpellier , Montpellier , France.
Vignone, Domenico
Fimia, Gian Maria
Valente, Enza Maria
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Title :
PINK1 and BECN1 relocalize at mitochondria-associated membranes during mitophagy and promote ER-mitochondria tethering and autophagosome formation.
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Landes Bioscience, United States - Texas
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Peer reviewed :
Peer Reviewed verified by ORBi


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