AGE-DEPENDENT DECLINE IN THE CYTOCHROME-C-OXIDASE ACTIVITY IN RAT-HEART MITOCHONDRIA - ROLE OF CARDIOLIPIN

Cardiolipin is a major mitochondrial membrane lipid and plays a pivota l role in mitochondrial function, We have recently suggested a possibl e involvement of this phospholipid in the age-linked decline of cytoch rome c oxidase activity in rat heart mitochondria [G. Paradies et al, (1993) Arch. Gerontol. Geriatr. 16, 263-272], The aim of this work was to test our earlier proposal, We have investigated whether addition o f exogenous cardiolipin to mitochondria is able to reverse, in situ, t he age-linked decrease in the cytochrome oxidase activity, The method of fusion of liposomes with mitochondria developed by Hackenbrock [Hac kenbrock and Chazotte (1986) Methods Enzymol. 125, 35-45] was employed in order to enrich the mitochondria cardiolipin content, We demonstra te that the lower cytochrome c oxidase activity in heart mitochondria from aged rats can be fully restored to the level of young control rat s by exogenously added cardiolipin. No restoration was obtained with o ther phospholipids or with peroxidized cardiolipin, Our data support a key role for cardiolipin in the age-linked decline of rat heart mitoc hondrial cytochrome c oxidase activity. (C) 1997 Federation of Europea n Biochemical Societies.