Mitochondria clearance during classical mitophagy can proceed independently of autophagosomes

Identification: Tan, Hayden



Mitochondria clearance during classical mitophagy can proceed independently of autophagosomes
Hayden Weng Siong Tan1,2, Han Ming Shen1,2
1NUS Graduate School for Integrative Sciences and Engineering
2Department of Physiology, National University of Singapore
Mitophagy is a selective autophagic process that is responsible for basal turnover of mitochondria, mitochondria clearance during specific development processes or the clearance of damaged mitochondria. PINK1-Parkin dependent or independent pathways exist to target whole mitochondria to the growing autophagosome membrane for auto-lysosomal degradation. Despite the current consensus for the requirement of autophagosomes in mitophagy, multiple reports have demonstrated that mitochondria clearance can occur in an autophagosome independent manner through various ATG knockout models, suggesting that alternative degradative pathways may exist for mitophagy. Here, we present some preliminary data for ATG-independent mitophagy using YFP-Parkin HeLa cells as a model for mitophagy. Degradation of various mitochondria markers induced by mitochondria depolarizing agents (e.g O/A: oligomycin + antimycin A) were not inhibited by knockdown of various ATGs. However, O/A-induced degradation of mitochondria markers was still dependent on lysosomal function as lysosome inhibitors impaired mitochondria protein degradation. O/A-induced mitochondria clearance was also not dependent on the ubiquitin-proteasome system as blockage of proteasomal degradation with MG132 did not impair degradation of mitochondria markers. Our current data suggest that mitochondria clearance induced by conventional mitophagy inducers can proceed in an autophagosome-independent manner.



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