PMID- 25961502
OWN - NLM
STAT- MEDLINE
DCOM- 20150831
LR  - 20240213
IS  - 1476-4679 (Electronic)
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 17
IP  - 6
DP  - 2015 Jun
TI  - Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy 
      facilitates lipolysis.
PG  - 759-70
LID - 10.1038/ncb3166 [doi]
AB  - 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.
FAU - Kaushik, Susmita
AU  - Kaushik S
AD  - 1] Department of Developmental and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, New York 10461, USA [2] Institute for Aging Studies, Albert 
      Einstein College of Medicine, Bronx, New York 10461, USA.
FAU - Cuervo, Ana Maria
AU  - Cuervo AM
AD  - 1] Department of Developmental and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, New York 10461, USA [2] Institute for Aging Studies, Albert 
      Einstein College of Medicine, Bronx, New York 10461, USA.
LA  - eng
GR  - R01 AG021904/AG/NIA NIH HHS/United States
GR  - P30 DK041296/DK/NIDDK NIH HHS/United States
GR  - AG031782/AG/NIA NIH HHS/United States
GR  - R37 AG021904/AG/NIA NIH HHS/United States
GR  - AG038072/AG/NIA NIH HHS/United States
GR  - P30 DK020541/DK/NIDDK NIH HHS/United States
GR  - P30 AG038072/AG/NIA NIH HHS/United States
GR  - P60 DK020541/DK/NIDDK NIH HHS/United States
GR  - R01 DK098408/DK/NIDDK NIH HHS/United States
GR  - P30 CA013330/CA/NCI NIH HHS/United States
GR  - DK098408/DK/NIDDK NIH HHS/United States
GR  - P01 AG031782/AG/NIA NIH HHS/United States
GR  - AG021904/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150511
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Carrier Proteins)
RN  - 0 (Fatty Acids)
RN  - 0 (HSC70 Heat-Shock Proteins)
RN  - 0 (Hspa8 protein, mouse)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Membrane Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Perilipin-2)
RN  - 0 (Perilipin-3)
RN  - 0 (Plin2 protein, mouse)
RN  - 0 (Plin2 protein, rat)
RN  - 0 (Plin3 protein, mouse)
RN  - EC 3.1.1.3 (Lipase)
RN  - EC 3.1.1.3 (PNPLA2 protein, mouse)
SB  - IM
CIN - Cell Metab. 2015 Jul 7;22(1):60-1. PMID: 26154053
MH  - 3T3 Cells
MH  - Animals
MH  - *Autophagy
MH  - Carrier Proteins/metabolism
MH  - Cell Line
MH  - Fatty Acids/metabolism
MH  - Fatty Liver/genetics
MH  - HSC70 Heat-Shock Proteins/metabolism
MH  - Lipase/metabolism
MH  - Lipid Droplets/*metabolism
MH  - Lipid Metabolism
MH  - *Lipolysis
MH  - Liver/*metabolism
MH  - Lysosomal-Associated Membrane Protein 2/genetics
MH  - Lysosomes/metabolism
MH  - Male
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Molecular Chaperones/*metabolism
MH  - Oxidation-Reduction
MH  - Perilipin-2
MH  - Perilipin-3
MH  - Protein Binding
MH  - Rats
MH  - Rats, Wistar
MH  - Starvation/metabolism
PMC - PMC4449813
MID - NIHMS675035
COIS- Competing Financial Interest The authors declare that they have no competing 
      interests.
EDAT- 2015/05/12 06:00
MHDA- 2015/09/01 06:00
PMCR- 2015/12/01
CRDT- 2015/05/12 06:00
PHST- 2014/12/16 00:00 [received]
PHST- 2015/03/23 00:00 [accepted]
PHST- 2015/05/12 06:00 [entrez]
PHST- 2015/05/12 06:00 [pubmed]
PHST- 2015/09/01 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - ncb3166 [pii]
AID - 10.1038/ncb3166 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2015 Jun;17(6):759-70. doi: 10.1038/ncb3166. Epub 2015 May 11.