PMID- 17404494
OWN - NLM
STAT- MEDLINE
DCOM- 20070830
LR  - 20231213
IS  - 1554-8627 (Print)
IS  - 1554-8627 (Linking)
VI  - 3
IP  - 4
DP  - 2007 Jul-Aug
TI  - Chaperone-mediated autophagy.
PG  - 295-9
AB  - Chaperone-mediated autophagy (CMA) is a lysosomal pathway of proteolysis that is 
      responsible for the degradation of 30% of cytosolic proteins under conditions of 
      prolonged nutrient deprivation. Molecular chaperones in the cytosol and in the 
      lysosomal lumen stimulate this proteolytic pathway. The molecular chaperones in 
      the cytosol unfold substrate proteins prior to their translocation across the 
      lysosomal membrane, while the chaperone in the lysosomal lumen is probably 
      required to pull the substrate protein across the lysosomal membrane. A critical 
      component for CMA is a receptor in the lysosomal membrane, the 
      lysosome-associated membrane protein (LAMP) type 2A. LAMP-2A levels in the 
      lysosomal membrane can be increased by reduced degradation and/or redistribution 
      from the lysosomal lumen to the lysosomal membrane. Recent results show that CMA 
      is also activated by oxidative stress, and in this case LAMP-2A is increased due 
      to transcriptional regulation. CMA can be reduced by inhibitors of 
      glucose-6-phosphate dehydrogenase and of the heat shock protein of 90 kDa. 
      Reduction of levels of LAMP-2A using RNAi strategies reduces CMA activity, but 
      macroautophagy is activated as a result. The decrease in CMA causes cells to be 
      more susceptibile to oxidative and other stresses. LAMP-2A in the lysosomal 
      membrane can be sequestered into cholesterol-rich microdomains where it is 
      inactive. When CMA is activated, LAMP-2A moves out of these domains. The reduced 
      CMA in aging is due to reduced LAMP-2A in the lysosomal membrane. This reduction 
      is caused by an age-related increased degradation of LAMP-2A and an age-related 
      reduced ability of LAMP-2A to reinsert into the lysosomal membrane. These 
      findings reveal a rich complexity of mechanisms to control CMA activity.
FAU - Dice, J Fred
AU  - Dice JF
AD  - Department of Cellular and Molecular Physiology, Tufts University School of 
      Medicine, Boston, MA 02111, USA. james.dice@tufts.edu
LA  - eng
GR  - AG06116/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20070715
PL  - United States
TA  - Autophagy
JT  - Autophagy
JID - 101265188
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Lysosomal Membrane Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Proteins)
SB  - IM
MH  - Autophagy/*physiology
MH  - HSP70 Heat-Shock Proteins/physiology
MH  - Heat-Shock Proteins/physiology
MH  - Lysosomal-Associated Membrane Protein 2/genetics/metabolism
MH  - Lysosomal Membrane Proteins
MH  - Lysosomes/metabolism
MH  - Models, Biological
MH  - Molecular Chaperones/*physiology
MH  - Proteins/physiology
RF  - 65
EDAT- 2007/04/04 09:00
MHDA- 2007/08/31 09:00
CRDT- 2007/04/04 09:00
PHST- 2007/04/04 09:00 [pubmed]
PHST- 2007/08/31 09:00 [medline]
PHST- 2007/04/04 09:00 [entrez]
AID - 4144 [pii]
AID - 10.4161/auto.4144 [doi]
PST - ppublish
SO  - Autophagy. 2007 Jul-Aug;3(4):295-9. doi: 10.4161/auto.4144. Epub 2007 Jul 15.