PINK1 and Parkin: emerging themes in mitochondrial homeostasis.
TLDR
Together with new insights in signal transduction, unique modalities and signatures of vertebrate mitophagy have been unravelled in vivo for the very first time and the cell biology of mammalianMitophagy has emerged to be more complex than previously thought.About:
This article is published in Current Opinion in Cell Biology.The article was published on 2017-04-01 and is currently open access. It has received 239 citations till now. The article focuses on the topics: Mitophagy & Parkin.read more
Citations
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Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand.
Thomas G. McWilliams,Alan R. Prescott,Lambert Montava-Garriga,Graeme Ball,François Singh,Erica Barini,Miratul M. K. Muqit,Simon Philip Brooks,Ian G. Ganley +8 more
TL;DR: These findings provide the first in vivo evidence that Pink1 is detectable at basal levels and that basal mammalian mitophagy occurs independently of PINK1, and suggest multiple, yet-to-be-discovered pathways orchestrating mammalian mitochondrial integrity in a context-dependent fashion.
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Mitostasis in Neurons: Maintaining Mitochondria in an Extended Cellular Architecture
TL;DR: Both long-range transport and local processing are at work in achieving neuronal mitostasis-the maintenance of an appropriately distributed pool of healthy mitochondria for the duration of a neuron's life.
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Diverse roles of mitochondria in ischemic stroke.
TL;DR: A better understanding of the roles of mitochondria in ischemia-related neuronal death and protection may provide a rationale for the development of innovative therapeutic regimens for ischemic stroke and other stroke syndromes.
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Autophagy: An Essential Degradation Program for Cellular Homeostasis and Life.
Yoomi Chun,Joungmok Kim +1 more
TL;DR: Dysregulation of autophagy is closely associated with a wide spectrum of human pathophysiological conditions including cancers and neurodegenerative diseases, and recent advances on the various post-translational modifications have shed light on the multiple layers of autophile regulatory mechanisms, and provide novel therapeutic targets for the treatment of the diseases.
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Reactive oxygen species trigger Parkin/PINK1 pathway-dependent mitophagy by inducing mitochondrial recruitment of Parkin.
TL;DR: It is demonstrated that the role of ROS in mitophagy has been underappreciated as a result of the inefficiency of ROS scavengers to control ROS bursts after high-dose treatment with carbonyl cyanide m-chlorophenylhydrazone and cast doubt on the importance of protein quantity of PINK1 in the recruitment of Parkin to mitochondria.
References
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The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy
Michael Lazarou,Danielle A. Sliter,Lesley A. Kane,Shireen A. Sarraf,Chunxin Wang,Jonathon L. Burman,Dionisia P. Sideris,Adam I. Fogel,Richard J. Youle +8 more
TL;DR: Using genome editing to knockout five autophagy receptors in HeLa cells, this work shows that two receptors previously linked to xenophagy, NDP52 and optineurin, are the primary receptors for PINK1- and parkin-mediated mitophagy.
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The Roles of PINK1, Parkin and Mitochondrial Fidelity in Parkinson's Disease
TL;DR: Biochemical and genetic studies reveal that the products of two genes that are mutated in autosomal recessive parkinsonism, PINK1 and Parkin, normally work together in the same pathway to govern mitochondrial quality control, bolstering previous evidence that mitochondrial damage is involved in Parkinson's disease.
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Ubiquitin is phosphorylated by PINK1 to activate parkin
Fumika Koyano,Kei Okatsu,Kei Okatsu,Hidetaka Kosako,Yasushi Tamura,Etsu Go,Mayumi Kimura,Yoko Kimura,Hikaru Tsuchiya,Hidehito Yoshihara,Takatsugu Hirokawa,Toshiya Endo,Edward A. Fon,Jean-François Trempe,Yasushi Saeki,Keiji Tanaka,Noriyuki Matsuda +16 more
TL;DR: The results show that PINK1-dependent phosphorylation of both parkin and ubiquitin is sufficient for full activation of parkin E3 activity, and demonstrate that phosphorylated ubiquit in is a parkin activator.
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PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity
Lesley A. Kane,Michael Lazarou,Adam I. Fogel,Yan Li,Koji Yamano,Shireen A. Sarraf,Soojay Banerjee,Richard J. Youle +7 more
TL;DR: PINK1 phosphorylates ubiquitin, which then binds to Parkin and activates its E3 ligase activity, leading to induction of selective autophagy of damaged mitochondria.
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Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy.
TL;DR: A model for selective autophagy formation in close proximity to cargo is proposed and found that UBLs can directly engage the autophagosome nucleation machinery.