Silencing of PINK1 induces mitophagy via mitochondrial permeability transition in dopaminergic MN9D cells.
Accumulation of dysfunctional Mitochondria has been implicated in the pathogenesis of Parkinson's disease (PD). Mutations in PTEN-induced kinase 1 (PINK1), which encodes a putative mitochondrial serine/threonine kinase, have been identified in early-onset forms of PD. Recent data showed that the loss of PINK1 function led to oxidative stress, mitochondrial damage and autophagic elimination of damaged mitochondria. But the precise mechanism of autophagy induced by loss of PINK1 is unclear. In this study, we found that in mouse dopaminergic MN9D cells, down-regulation of PINK1 by RNA interference resulted in induction of mitochondrial autophagy (mitophagy), abnormal mitochondrial morphology, partial loss of mitochondrial membrane potential and increased production of reactive oxygen species (ROS). Mitophagy in these cells was associated with the up-regulation of autophagy activator Beclin 1 and opening of mitochondrial permeability transition (MPT) pore. These findings suggest that PINK1 may regulate mitophagy through controlling MPT pore opening and general autophagy regulators.
Beijing Institute for Neuroscience, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing 100069, China.
Tao
T
Cui
Chunxiang
C
Fan
Li
L
Gu
Hua
H
Gao
Qi
Q
Liu
Tao
T
Zhang
Zhifeng
Z
Qi
Chunli
C
Zhao
Huanying
H
Zhao
Qing
Q
Cai
Hui
H
Yang
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D053078:Membrane Potential, Mitochondrial / Q000502:physiology*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism*; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000099202:PTEN-Induced Putative Kinase
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011494:Protein Kinases; D017382:Reactive Oxygen Species; D000099202:PTEN-Induced Putative Kinase