PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin

By Derek P. Narendra, S. Jin, Atsushi Tanaka, D. Suen, C. Gautier, Jie Shen, M. Cookson, R. Youle. PLoS Biology, 2010

2,915 citations recorded by the source corpus.

Mutations in PINK1 or Parkin lead to familial parkinsonism. The authors suggest that PINK1 and Parkin form a pathway that senses damaged mitochondria and selectively targets them for degradation.

Subfields: Epidemiology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/12c498eb0a66933ca662e6d0135b934935f137c2

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Citations in the corpus

Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control (2014, methodology): “…paradigm, PINK1, a serine/threonine kinase, globally accumulates on depolarized mitochondria and recruits parkin from the cytosol to mitochondria in a manner dependent upon PINK1 phosphorylation activity (Narendra et al, 2008, 2010; Matsuda et al, 2010; Vives-Bauza et al, 2010; Greene et al, 2012).”
Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin (2010, methodology): “In contrast to inhibition of transcription, inhibition of translation by treatment which translocates to depolarized mitochondria but fails to induce mitophagy; and Parkin, which fails to translocate to mitochondria (Narendra et al., 2010).”
Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences (2012, positive): “…import and processing by PARL is inhibited, leading to the integration of PINK1 into the outer mitochondrial membrane, which is a prerequisite to recruit parkin for the induction of mitophagy (Jin et al , 2010; Matsuda et al , 2010; Narendra et al , 2010b; Meissner et al , 2011) (see below).”
Mitochondria and Mitophagy: The Yin and Yang of Cell Death Control (2012, background): “Studies have demonstrated that the expression of PINK1 is necessary for the recruitment of Parkin to depolarized mitochondria.(92,94) However, exactly how accumulation of PINK1 on the outer mitochondrial membrane results in recruitment and activation of Parkin is currently unclear.”
Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells (2012, methodology): “(c) HeLa cells were transfected with (Flag)N-Fundc1(1-155)-C(Myc) or (Flag)N-Fundc1(1-139)C(Myc) vectors, respectively.”
Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin (2012, background): “In healthy mitochondria, PINK1 levels are kept low through membrane potential dependent import and constitutive turn over (Jin et al., 2010; Narendra et al., 2010b).”
Mitochondrial Dysfunction in Parkinson's Disease (2011, background): “The proposed model suggests that in response to mitochondrial depolarization PINK1 accumulates on the mitochondrial membrane and recruits Parkin to promote mitophagy [78, 79].”
PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy (2010, result): “While our manuscript was under review, Geisler et al. (2010), Narendra et al. (2010), and Vives-Bauza et al. (2010) independently published results that are consistent with those described herein.”
Mitochondria: In Sickness and in Health (2012, background): “Loss of membrane potential inhibits the degradation of PINK1 and reroutes it to the surfaceofmitochondria,where it accumulatesand recruitsParkin (Kim et al., 2008; Lin and Kang, 2008; Matsuda et al., 2010; Narendra et al., 2010; Vives-Bauza et al., 2010; Ziviani et al., 2010).”
Mitochondrial fusion and fission in cell life and death (2010, background): “PINK1 is a protein kinase that is selectively stabilized in mitochondria with low membrane potential, where it recruits Parkin to mark impaired mitochondria and promote mitophag”