Mechanisms of chaperone-mediated autophagy.
Chaperone-mediated autophagy is one of several lysosomal pathways of proteolysis. This pathway is activated by physiological stresses such as prolonged starvation. Cytosolic proteins with particular peptide sequence motifs are recognized by a complex of molecular chaperones and delivered to lysosomes. No vesicular traffic is required for this protein degradation pathway, so it differs from microautophagy and macroautophagy. Protein substrates bind to a receptor in the lysosomal membrane, the lysosome-associated membrane protein (lamp) type 2a. Levels of lamp2a in the lysosomal membrane are controlled by alterations in the lamp2a half-life as well as by the dynamic distribution of the protein between the lysosomal membrane and the lumen. Substrate proteins are unfolded before transport into the lysosome lumen, and the transport of substrate proteins requires a molecular chaperone within the lysosomal lumen. The exact roles of this lysosomal chaperone remain to be defined. The mechanisms of chaperone-mediated autophagy are similar to mechanisms of protein import into mitochondria, chloroplasts, and the endoplasmic reticulum.
Department of Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA. amy.majeski@tufts.edu
Amy E
AE
Majeski
J Fred
JF
Dice
D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D003600:Cytosol / Q000502:physiology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*
D015703:Antigens, CD; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D051907:Lysosomal Membrane Proteins; D018832:Molecular Chaperones; D011506:Proteins