Chaperone-like protein p32 regulates ULK1 stability and autophagy.

Mitophagy mediates clearance of dysfunctional mitochondria, and represents one type of mitochondrial quality control, which is essential for optimal mitochondrial bioenergetics. p32, a chaperone-like protein, is crucial for maintaining mitochondrial membrane potential and oxidative phosphorylation. However, the relationship between p32 and mitochondrial homeostasis has not been addressed. Here, we identified ...
p32 as a key regulator of ULK1 stability by forming complex with ULK1. p32 depletion potentiated K48-linked but impaired K63-linked polyubiquitination of ULK1, leading to proteasome-mediated degradation of ULK1. As a result, silencing p32 profoundly impaired starvation-induced autophagic flux and the clearance of damaged mitochondria caused by mitochondrial uncoupler. Importantly, restoring ULK1 expression in p32-depleted cells rescued autophagy and mitophagy defects. Our findings highlight a cytoprotective role of p32 under starvation conditions by regulating ULK1 stability, and uncover a crucial role of the p32-ULK1-autophagy axis in coordinating stress response, cell survival and mitochondrial homeostasis.
Mesh Terms:
Autophagy, Autophagy-Related Protein-1 Homolog, Cell Line, Flow Cytometry, HCT116 Cells, HEK293 Cells, HeLa Cells, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins, Polyubiquitin, Proteasome Endopeptidase Complex, Protein Serine-Threonine Kinases, Protein Stability, Receptors, Complement
Cell Death Differ
Date: Nov. 01, 2015
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