Omegasome-proximal PtdIns(4,5)P2 couples F-actin mediated mitoaggregate disassembly with autophagosome formation during mitophagy

Nature Communications
Cheng-Wei Hsieh, Wei Yuan Yang

Abstract

Cells govern their homeostasis through autophagy by sequestering substrates, ranging from proteins to aggregates and organelles, into autophagosomes for lysosomal degradation. In these processes cells need to coordinate between substrate remodeling and autophagosome formation for efficient engulfment. We found that in Parkin-mediated mitophagy, mitochondria to be turned over first become grape-like mitoaggregates, followed by their disassembly into smaller pieces via the actinomyosin system. At the disassembly step, we observed spatially-associated, synchronous formation of circular F-actin and BATS-labeled autophagy initiation sites near mitochondria, suggesting coordination between substrate downsizing and autophagosome formation during mitophagy. Interestingly, PtdIns(4,5)P2, instead of PtdIns(3)P, regulates this mitophagy-associated formation of circular F-actin and BATS-sites. Selective depletion of PtdIns(4,5)P2 near omegasomes, the endoplasmic reticulum (ER) subdomains involved in autophagosome formation, impaired mitoaggregate disassembly. Our findings demonstrate the presence of a pool of PtdIns(4,5)P2 adjacent to omegasomes, and that they coordinate mitoaggregate disassembly with autophagy initiation during Parkin-med...Continue Reading

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Citations

Apr 8, 2020·Frontiers in Cell and Developmental Biology·Maria Zachari, Nicholas T Ktistakis
Oct 30, 2020·The Journal of Clinical Investigation·Meagan J McGrathChristina A Mitchell
Nov 11, 2019·Journal of Molecular Biology·Simon A Walker, Nicholas T Ktistakis
Apr 2, 2021·Plant Physiology·Abel Rosado, Emmanuelle M Bayer
Apr 30, 2021·Journal of Cell Science·Antonina J Kruppa, Folma Buss
Oct 15, 2021·Cell Death & Disease·Qixin ChenJiajie Diao

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Methods Mentioned

BETA
ubiquitination
electron microscopy
fluorescence microscopy
PCR

Software Mentioned

Image
Image J
CLEM
EGFP
LifeAct

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