Alternative mitochondrial quality control mediated by extracellular release.

Autophagy
Chi-Jing ChoongHideki Mochizuki

Abstract

Mitochondrial quality control, which is crucial for maintaining cellular homeostasis, has been considered to be achieved exclusively through mitophagy. Here we report an alternative mitochondrial quality control pathway mediated by extracellular mitochondria release. By performing time-lapse confocal imaging on a stable cell line with fluorescent-labeled mitochondria, we observed release of mitochondria from cells into the extracellular space. Correlative light-electron microscopy revealed that majority of the extracellular mitochondria are in free form and, on rare occasions, some are enclosed in membrane-surrounded vesicles. Rotenone- and carbonyl cyanide m-chlorophenylhydrazone-induced mitochondrial quality impairment promotes the extracellular release of depolarized mitochondria. Overexpression of PRKN (parkin RBR E3 ubiquitin protein ligase), which has a pivotal role in mitophagy regulation, suppresses the extracellular mitochondria release under basal and stress condition, whereas its knockdown exacerbates it. Correspondingly, overexpression of PRKN-independent mitophagy regulators, BNIP3 (BCL2 interacting protein 3) and BNIP3L/NIX (BCL2 interacting protein 3 like), suppress extracellular mitochondria release. Autophagy-d...Continue Reading

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Citations

Jan 17, 2021·International Journal of Molecular Sciences·Enrique MadrugaAna Martínez
Feb 21, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yang ChenBin Shen
Apr 4, 2021·Biology·Govinda SharmaTimothy E Shutt
Aug 10, 2021·DNA and Cell Biology·Yu XuZhenglu Shang

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Methods Mentioned

BETA
GTPase
ubiquitination
biopsies
transfection
PCR

Software Mentioned

MASCOT
GraphPad Prism
ImageJ
IN Cell Developer Toolbox

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