p62-Mediated mitochondrial clustering attenuates apoptosis induced by mitochondrial depolarization
Autor: | Kah-Leong Lim, Bin Xiao, Zhi Dong Zhou, Xiao Deng, Wei Zhou, Eng-King Tan, Wuan-Ting Saw, Grace Lim |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Ubiquitin-Protein Ligases Apoptosis Mitochondrion Biology Mitochondrial apoptosis-induced channel Parkin 03 medical and health sciences 0302 clinical medicine Sequestosome-1 Protein Mitophagy Humans Molecular Biology Membrane Potential Mitochondrial Cytochromes c Cell Biology Mitochondria nervous system diseases Cell biology HEK293 Cells 030104 developmental biology Mitochondrial permeability transition pore Mitochondrial Membranes Proteolysis DNAJA3 Apoptosis-inducing factor 030217 neurology & neurosurgery HeLa Cells |
Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1864:1308-1317 |
ISSN: | 0167-4889 |
Popis: | Parkin/PINK1-mediated mitophagy is implicated in the pathogenesis of Parkinson's disease (PD). Prior to elimination of damaged mitochondria, Parkin translocates to mitochondria and induces mitochondrial clustering. While the mechanism of PINK1-dependent Parkin redistribution to mitochondria is now becoming clear, the role of mitochondrial clustering has been less well understood. In our study, we found that loss of p62 disrupted mitochondrial aggregation and specifically sensitized Parkin-expressing cells to apoptosis induced by mitochondrial depolarization. Notably, altering mitochondrial aggregation through regulating p62 or other methods was sufficient to affect such apoptosis. Moreover, disruption of mitochondrial aggregation promoted proteasome-dependent degradation of outer mitochondrial membrane (OMM) proteins. The accelerated degradation in turn facilitated cytochrome c release from mitochondria, leading to apoptosis. Together, our study demonstrates a protective role of mitochondrial clustering in mitophagy and helps in understanding how aggregation defends cells against stress. |
Databáze: | OpenAIRE |
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