Evidence for an in vivo modification of mitochondrial proteins by coenzyme A.
Following denaturation of mitochondrial proteins by sodium dodecyl sulfate, a [1-14C]pantothenic acid-derived radioactivity proved to be acid precipitable in the outer membrane, the intermembrane space, the inner membrane and in the matrix of rat liver mitochondria, where it had the highest specific radioactivity of 541 +/- 29 cpm/100 micrograms protein. This tightly and/or covalently bound protein radioactivity could be released by incubation in the presence of dithioerythreitol; it was identified as [14C]coenzyme A by its HPLC retention time, its absorption spectrum and its radioactivity. This acid-stable and thiol-labile coenzyme A-binding apparently refers to specific protein binding sites. With the purified, homogeneous mitochondrial matrix enzymes acetyl-CoA acetyltransferase (acetoacetyl-CoA thiolase) (EC 2.3.1.9, acetyl-CoA:acetyl-CoA C-acetyltransferase) and 3-oxoacyl-CoA thiolase (EC 2.3.1.16) coenzyme A was found exclusively, e.g., in the modified, partially-active forms A1 und A2 of acetyl-CoA acetyltransferase and not in the unmodified fully-active enzyme. Thus it is evident that this coenzyme A modification is transient. We suggest that coenzyme A-modification is a signal involved in the assembly or the degradation process of distinct mitochondrial matrix proteins.
Huth
W
W
Institut für Biochemie, Fachbereich Medizin, Georg-August Universität Göttingen, F.R.G.
Worm-Breitgoff
C
C
Möller
U
U
Wunderlich
I
I
D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism; D000102:Acetyl-CoA C-Acyltransferase / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D002458:Cell Fractionation; D003065:Coenzyme A / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010205:Pantothenic Acid / Q000378:metabolism*; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013367:Submitochondrial Particles / Q000378:metabolism
D002250:Carbon Radioisotopes; D011506:Proteins; D010205:Pantothenic Acid; D000102:Acetyl-CoA C-Acyltransferase; D000101:Acetyl-CoA C-Acetyltransferase; D003065:Coenzyme A