Regulation of the activity of branched-chain 2-oxo acid dehydrogenase (BCODH) complex by binding BCODH kinase

Branched-chain 2-oxo acid dehydrogenase (BCODH) kinase is responsible for i nactivation of BCODH complex by phosphorylation of the complex. Activity of the kinase towards its substrate, the El component of the BCODH complex, i s known dependent upon binding of the kinase to the E2 component, The possi ble existence as well as importance of unbound mitochondrial BCODH kinase h as been largely ignored in previous studies, Evidence is presented here for the existence of free and bound BCODH kinase in the matrix space of rat li ver mitochondria, Furthermore, in female rats, in which diurnal variations in liver BCODH complex and kinase activities occur, the amount of the kinas e bound to the complex changes between morning and evening without a change in total kinase protein, Activity of the kinase correlates with the amount of bound rather than total kinase protein, suggesting only the bound form is active. Changes in amount of kinase bound and therefore active appear re sponsible for diurnal variation in BCODH complex activity in the female rat , We propose that change in the amount of bound BCODH kinase is a kev featu re of a novel regulatory mechanism for determining the activity state of th e BCODH complex. (C) 2001 Federation of European Biochemical Societies. Pub lished by Elsevier Science B,V, All rights reserved.