Regulation of the mitochondrial ATP-synthase in human fibroblasts.
The F1F0-ATPase activity of mitochondrial complex V can be rapidly measured in sonicated preparations of monolayer skin fibroblast cultures from children. We show that direct regulation at the level of ATP-synthase occurs in these cell preparations. ATP-synthase capacity is decreased in response to blocking of the respiratory chain by cyanide (mimicking anoxia) or uncoupling of mitochondria. ATP-synthase capacity falls to 60% and 35% of control, respectively. Up-regulation of ATP-synthase can be demonstrated in fibroblasts exposed to 4 mmol/l calcium (127% of control). Mitochondrial recovery was unchanged under the different incubation conditions as judged by the activity of mitochondrial marker enzymes. We conclude that direct regulation at the level of ATP-synthase occurs in vivo in human fibroblasts. The naturally occurring inhibitor protein IF1 and the calcium binding inhibitor protein CaBI may be involved in this regulation of ATP-synthase.
Das
A M
AM
Department of Pediatric Nephrology and Metabolic Disorders, Children's Hospital, Hannover Medical School, Germany.
Byrd
D J
DJ
Brodehl
J
J
D000293:Adolescent; D002118:Calcium / Q000494:pharmacology; D002648:Child; D003486:Cyanides / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008928:Mitochondria / Q000201:enzymology; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D015854:Up-Regulation
D003486:Cyanides; D006180:Proton-Translocating ATPases; D002118:Calcium