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Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis

Open access
Kaushik, Susmita, Cuervo, Ana Maria·2015·Nature Cell Biology

Abstract

Chaperone-mediated autophagy (CMA) selectively degrades a subset of cytosolic proteins in lysosomes. A potent physiological activator of CMA is nutrient deprivation, a condition in which intracellular triglyceride stores or lipid droplets (LDs) also undergo hydrolysis (lipolysis) to generate free fatty acids for energetic purposes. Here we report that the LD-associated proteins perilipin 2 (PLIN2) and perilipin 3 (PLIN3) are CMA substrates and their degradation through CMA precedes lipolysis. In vivo studies revealed that CMA degradation of PLIN2 and PLIN3 was enhanced during starvation, concurrent with elevated levels of cytosolic adipose triglyceride lipase (ATGL) and macroautophagy proteins on LDs. CMA blockage both in cultured cells and mouse liver or expression of CMA-resistant PLINs leads to reduced association of ATGL and macrolipophagy-related proteins with LDs and the subsequent decrease in lipid oxidation and accumulation of LDs. We propose a role for CMA in LD biology and in the maintenance of lipid homeostasis.

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Metadata

Authors
Kaushik, S., & Cuervo, A. M.
Venue
Nature Cell Biology
Published
2015-05-11
Volume
17
Issue
6
Pages
759-770
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
OpenAlex
W1706150252
Cited by
714
References
4
FWCI
34.17
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis. https://app.cochat.ai/papers/10.1038/ncb3166
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Kaushik, S., & Cuervo, A. M. (2015). Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis. Nature Cell Biology. https://doi.org/10.1038/ncb3166

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