ATP and 2,3-bisphosphoglycerate: models of metabolites for the regulation of intracellular protein degradation.
The main question in protein turnover is what determines the susceptibility of a given protein molecule to proteolytic degradation. Much evidence supports a role for the structural characteristics of individual proteins in determining their specific degradation rates. However, changes in the environment can influence these characteristics and thus the degradation rates. Since intracellular proteins in vivo are in a natural environment, substrates, products, cofactors and other low molecular weight compounds are often bound to the proteins, and probably contribute thereby to the vastly different half-lives of proteins. This paper reviews recent results from the authors' laboratory on the possible regulation of intracellular protein degradation by low molecular weight components. We have centered our studies on 2,3-bisphosphoglycerate and ATP, which modify, in opposite directions, the proteolytic susceptibility of specific mitochondrial and cytosolic proteins to lysosomal and non-lysosomal proteases. As shown, these metabolites can also modify the microautophagic uptake of certain proteins as well as the degradation rate of proteins in cultured cells.
Roche
E
E
Instituto de Investigaciones Citológicas de la Caja de Ahorros de Valencia, Centro Asociado del C.S.I.C., Spain.
Aniento
F
F
Knecht
E
E
D019794:2,3-Diphosphoglycerate; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001343:Autophagy; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004163:Diphosphoglyceric Acids / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009954:Ornithine Carbamoyltransferase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004163:Diphosphoglyceric Acids; D011506:Proteins; D019794:2,3-Diphosphoglycerate; D000255:Adenosine Triphosphate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D009954:Ornithine Carbamoyltransferase