Restricted mitochondrial protein acetylation initiates mitochondrial autophagy
Copyright policy )Restricted mitochondrial protein acetylation initiates mitochondrial autophagy
As nutrient-sensing nuclear/cytosolic acetylation mediates cellular autophagy, we investigated whether mitochondrial acetylation modulates mitochondrial autophagy. Knockdown of GCN5L1, a component of the mitochondrial acetyltransferase machinery, diminished mitochondrial protein acetylation and augmented mitochondrial enrichment of autophagy mediators. This program was disrupted by Sirt3 knockdown. Chronic GCN5L1 depletion increased mitochondrial turnover and reduced mitochondrial protein content/mass. In parallel, mitochondria showed blunted respiration and enhanced ‘stress-resilience’. Genetic disruption of autophagy mediators Atg5 and p62, as well as GCN5L1 reconstitution, abolished deacetylation-induced mitochondrial autophagy. Interestingly, this program is independent of the mitophagy E3-ligase Parkin. Together these data support that deacetylation of mitochondrial proteins initiate mitochondrial autophagy in a canonical autophagy mediator-dependent program and shows that modulation of this regulatory program has ameliorative mitochondrial homeostatic effects.
- National Institute of Health Pakistan
- Center for Molecular Medicine and Immunology United States
Male, Mice, Knockout, Ubiquitin-Protein Ligases, Acetylation, Nerve Tissue Proteins, Mitochondria, Mice, Inbred C57BL, Mitochondrial Proteins, Mice, HEK293 Cells, Autophagy, Animals, Humans, HeLa Cells
Male, Mice, Knockout, Ubiquitin-Protein Ligases, Acetylation, Nerve Tissue Proteins, Mitochondria, Mice, Inbred C57BL, Mitochondrial Proteins, Mice, HEK293 Cells, Autophagy, Animals, Humans, HeLa Cells
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