Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL

By S. Jin, M. Lazarou, Chunxin Wang, L. A. Kane, Derek P. Narendra, R. Youle. Journal of Cell Biology, 2010

1,343 citations recorded by the source corpus.

Differential localization to the inner and outer mitochondrial membranes regulates PINK1 stability and function.

Subfields: Epidemiology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/a612d8e60fc8d29619b97b252579f4ce9e1e4604

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Citations in the corpus

PINK1- and Parkin-mediated mitophagy at a glance (2012, background): “…for TIM-mediated mitochondrial import of proteins – PINK1 no longer becomes processed by either MPP or PARL and the fulllength 64-kDa form rapidly accumulates, spanning the OMM with its kinase domain facing the cytosol (Jin et al., 2010; Narendra et al., 2010b) (Poster Panel 2, lower part).”
Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences (2012, positive): “PARL (presenilin-associated rhomboid like protease) has recently been identiﬁed as a protease promoting PINK1 cleavage under basal conditions to keep mitochondrial PINK1 levels low (Whitworth et al , 2008; Jin et al , 2010; Deas et al , 2011; Meissner et al , 2011; Shi et al , 2011).”
Quantitative proteomics reveal a feed-forward model for mitochondrial PARKIN translocation and UB chain synthesis (2014, positive): “PINK1 is imported into mitochondria via the translocon of the outer membrane (TOM) complex and in healthy mitochondria is rapidly degraded (Jin et al., 2010; Lazarou et al., 2012).”
Mitochondrial dynamics in health and disease: mechanisms and potential targets (2023, background): “130 The PINK1/Parkin pathway is activated when the mitochondria undergo a depolarizing condition, leading to the recruitment of Parkin under stress and the disposal of damaged mitochondria through autophagy.”
Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease (2012, background): “In healthy mitochondria, PINK1 levels are kept low through membrane potential-dependent import and constitutive cleavage by the mitochondrial rhomboid protease PARL in the inner membrane followed by subsequent degradation by an MG132-sensitive protease [166,167].”
Deciphering the Molecular Signals of PINK1/Parkin Mitophagy. (2016, background): “Next, the rhomboid protease presenilin-associated rhomboid like (PARL) cleaves PINK1 between amino acids A103 and F104 in its hydrophobic domain spanning the IMM [81–83].”
An Overview of Autophagy: Morphology, Mechanism, and Regulation (2014, background): “This prevents the accumulation of PINK1 on the mitochondrial outer membrane, which would otherwise lead to mitophagy of healthy mitochondria (61, 98).”
Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin (2012, background): “We have previously shown that PINK1 is imported into mitochondria and constitutively turned over in a PARL mediated process that requires mitochondrial membrane potential (Jin et al., 2010).”
MitoFates: Improved Prediction of Mitochondrial Targeting Sequences and Their Cleavage Sites (2015, background): “PINK1 is rapidly degraded in healthy mitochondria but accumulates on the surface of membrane potential deficient mitochondria where it recruits parkin to ubiquitylate the damaged mitochondria (59–62).”
The Roles of PINK1, Parkin and Mitochondrial Fidelity in Parkinson's Disease (2015, background): “…constitutive degradation of PINK1 in healthy mitochondria within a cell, which is circumvented when one mitochondrion becomes impaired, allowing PINK1 to accumulate on the outer membrane of the dysfunctional mitochondrion (Jin et al., 2010; Meissner et al., 2011; Narendra et al., 2010b; Figure 4).”
A new pathway for mitochondrial quality control: mitochondrial‐derived vesicles (2014, background): “PLoS ONE 6: e17285 Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ (2010) Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL.”
Mitophagy: mechanisms, pathophysiological roles, and analysis (2012, background): “However, Pink1 is stabilized on the outer mitochondrial membrane and forms a large complex with the translocase of the outer membrane where it can recruit Parkin to impaired mitochondria when mitochondrial membrane potential is dissipated (Jin et al. , 2010 ; Lazarou et al. , 2012 ).”