PMID- 15883160
OWN - NLM
STAT- MEDLINE
DCOM- 20050816
LR  - 20231213
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 27
DP  - 2005 Jul 8
TI  - Ketone bodies stimulate chaperone-mediated autophagy.
PG  - 25864-70
AB  - Chaperone-mediated autophagy (CMA) is a selective lysosomal protein degradative 
      process that is activated in higher organisms under conditions of prolonged 
      starvation and in cell culture by the removal of serum. Ketone bodies are 
      comprised of three compounds (beta-hydroxybutyrate, acetoacetate, and acetone) 
      that circulate during starvation, especially during prolonged starvation. Here we 
      have investigated the hypothesis that ketone bodies induce CMA. We found that 
      physiological concentrations of beta-hydroxybutyrate (BOH) induced proteolysis in 
      cells maintained in media with serum and without serum; however, acetoacetate 
      only induced proteolysis in cells maintained in media with serum. Lysosomes 
      isolated from BOH-treated cells displayed an increased ability to degrade both 
      glyceraldehyde-3-phosphate dehydrogenase and ribonuclease A, substrates for CMA. 
      Isolated lysosomes from cells maintained in media without serum also demonstrated 
      an increased ability to degrade glyceraldehyde-3-phosphate dehydrogenase and 
      ribonuclease A when the reaction was supplemented with BOH. Such treatment did 
      not affect the levels of lysosome-associated membrane protein 2a or lysosomal 
      heat shock cognate protein of 70 kDa, two rate-limiting proteins in CMA. However, 
      pretreatment of glyceraldehyde-3-phosphate and ribonuclease A with BOH increased 
      their rate of degradation by isolated lysosomes. Lysosomes pretreated with BOH 
      showed no increase in proteolysis, suggesting that BOH acts on the substrates to 
      increase their rates of proteolysis. Using OxyBlot analysis to detect carbonyl 
      formation on proteins, one common marker of protein oxidation, we showed that 
      treatment of substrates with BOH increased their oxidation. Neither glycerol, 
      another compound that increases in circulation during prolonged starvation, nor 
      butanol or butanone, compounds closely related to BOH, had an effect on CMA. The 
      induction of CMA by ketone bodies may provide an important physiological 
      mechanism for the activation of CMA during prolonged starvation.
FAU - Finn, Patrick F
AU  - Finn PF
AD  - Department of Molecular and Cellular Physiology, Tufts University School of 
      Medicine, Boston, Massachusetts 02111, USA. Patrick.Finn@tufts.edu
FAU - Dice, J Fred
AU  - Dice JF
LA  - eng
PT  - Journal Article
DEP - 20050509
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, CD)
RN  - 0 (Blood Proteins)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Ketone Bodies)
RN  - 0 (Lysosomal Membrane Proteins)
RN  - 0 (Molecular Chaperones)
SB  - IM
MH  - Antigens, CD/metabolism
MH  - Autophagy/*drug effects/*physiology
MH  - Blood Proteins/pharmacology
MH  - Cells, Cultured
MH  - Culture Media, Serum-Free/pharmacology
MH  - Fibroblasts/*cytology/drug effects
MH  - HSP70 Heat-Shock Proteins/metabolism
MH  - Humans
MH  - Ketone Bodies/*pharmacology
MH  - Lysosomal Membrane Proteins
MH  - Lysosomes/metabolism
MH  - Molecular Chaperones/*metabolism
MH  - Oxidation-Reduction
EDAT- 2005/05/11 09:00
MHDA- 2005/08/17 09:00
CRDT- 2005/05/11 09:00
PHST- 2005/05/11 09:00 [pubmed]
PHST- 2005/08/17 09:00 [medline]
PHST- 2005/05/11 09:00 [entrez]
AID - S0021-9258(20)61402-8 [pii]
AID - 10.1074/jbc.M502456200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Jul 8;280(27):25864-70. doi: 10.1074/jbc.M502456200. Epub 2005 
      May 9.