Asset Details
Do you wish to reserve the book?
PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin
Do you wish to request the book?
PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin
2010
Overview
Loss-of-function mutations in PINK1 and Parkin cause parkinsonism in humans and mitochondrial dysfunction in model organisms. Parkin is selectively recruited from the cytosol to damaged mitochondria to trigger their autophagy. How Parkin recognizes damaged mitochondria, however, is unknown. Here, we show that expression of PINK1 on individual mitochondria is regulated by voltage-dependent proteolysis to maintain low levels of PINK1 on healthy, polarized mitochondria, while facilitating the rapid accumulation of PINK1 on mitochondria that sustain damage. PINK1 accumulation on mitochondria is both necessary and sufficient for Parkin recruitment to mitochondria, and disease-causing mutations in PINK1 and Parkin disrupt Parkin recruitment and Parkin-induced mitophagy at distinct steps. These findings provide a biochemical explanation for the genetic epistasis between PINK1 and Parkin in Drosophila melanogaster. In addition, they support a novel model for the negative selection of damaged mitochondria, in which PINK1 signals mitochondrial dysfunction to Parkin, and Parkin promotes their elimination.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Humans
/ Membrane Potential, Mitochondrial
/ Metalloproteases - metabolism
/ Mice
/ Mitochondrial Membranes - metabolism
/ Mutation
/ Neurological Disorders/Movement Disorders
/ Neuroscience/Neurobiology of Disease and Regeneration
/ Parkinson Disease - genetics
/ Protein Kinases - metabolism
/ Proteins
/ Rats
