A mitochondrial protease that cleaves the precursor of ornithine carbamoyltransferase. Purification and properties.

Abstract

Ornithine carbamoyltransferase of rat liver mitochondrial matrix (subunit Mr = 36,000) is synthesized extra-mitochondrially as a larger precursor (subunit Mr = 39,400) which is transported into mitochondria, in association with post-translational proteolytic processing. Rat liver mitochondria convert the precursor to the mature enzyme as well as to a 37,000-Mr product, a possible intermediate of the processing [Mori, M., Miura, S., Tatibana, M., and Cohen, P.P. (1980) Proc. Natl Acad. Sci. USA, 77, 7044-7048]. A protease responsible for the conversion of the precursor to the 37,000-Mr product was purified 140-fold from the matrix fraction of rat liver mitochondria. The protease had an estimated Mr of 108,000 and an apparent pI of 5.5. Mature ornithine carbamoyltransferase (0.5 microgram) did not inhibit the cleavage of the precursor by the protease and presumably the latter cleaves a specific site on the extrapeptide of the carbamoyltransferase precursor. The protease was inhibited by metal-chelating reagents such as EDTA, o-phenanthroline and zincon and by a high concentration (1 mM) of leupeptin. It did not cleave several of the protein and peptide substrates tested including the precursor of mitochondrial carbamoyl-phosphate synthetase I. Apparently the same protease activity is widely distributed among mitochondria of rat kidney, spleen, heart and ascites tumor cells, all of which lack ornithine carbamoyltransferase. A possible physiological role of the protease in the processing of the mitochondrial protein precursors is discussed.

• Authors: S Miura, M Mori, Y Amaya, M Tatibana
• Journal: European journal of biochemistry (Eur J Biochem) Vol. 122 Issue 3 Pg. 641-7 (Mar 01 1982) ISSN: 0014-2956 [Print] England
• PMID: 7037411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Precursors
• Ornithine Carbamoyltransferase
• Peptide Hydrolases

Topics

• Animals
• Chemical Phenomena
• Chemistry
• Enzyme Precursors (metabolism)
• Kinetics
• Male
• Mice
• Mitochondria (enzymology)
• Molecular Weight
• Ornithine Carbamoyltransferase (metabolism)
• Peptide Hydrolases (isolation & purification, metabolism)
• Rats
• Rats, Inbred Strains