Cooperation of lysosomes and inner mitochondrial membrane in the degradation of carbamoyl phosphate synthetase and other proteins.
Carbamoyl phosphate synthetase (CPS) from rat liver is proteolitically inactivated at acid pH by broken lysosomes. Inactivation increases when lysosomes are previously incubated with inner mitochondrial membrane, although this mitochondrial fraction does not inactivate CPS 'per se'. The increased degradation is due to membrane factor(s), most probably mitochondrial proteinase(s), solubilized by lysosomal matrix proteinases, after incubation of the inner mitochondrial membrane fraction with broken lysosomes. This (these ) factor(s) degrade(s) CPS and other proteins in the absence of lysosomal proteinases or when these are inhibited by leupeptin, chymostatin and pepstatin. We have also tested the possible regulation of this degradation and found that ATP and, particularly, acetyl glutamate accelerate the degradation of CPS by the factor(s) liberated from the inner mitochondrial membrane.
Instituto de Investigaciones Citológicas de la Caja de Ahorros de Valencia, Centro Asociado del C.S.I.C., Valencia, Spain.
J L
JL
Vargas
E
E
Knecht
J
J
Hernández-Yago
S
S
Grisolía
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000378:metabolism*; D004789:Enzyme Activation; D005971:Glutamates / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000201:enzymology*; D007976:Leupeptins / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D009842:Oligopeptides / Q000494:pharmacology; D010436:Pepstatins / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D013379:Substrate Specificity
D005971:Glutamates; D007976:Leupeptins; D009842:Oligopeptides; D010436:Pepstatins; D011480:Protease Inhibitors; C014195:Streptomyces pepsin inhibitor; D000255:Adenosine Triphosphate; C002101:chymostatin; D010447:Peptide Hydrolases; D002222:Carbamoyl-Phosphate Synthase (Ammonia); C032854:leupeptin; C016195:N-acetylglutamic acid; C031375:pepstatin