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 pivotal role in mitochondrial function. We have recently suggested a possible involvement of this phospholipid in the age-linked decline of cytochrome 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 of exogenous cardiolipin to mitochondria is able to reverse, in situ, the age-linked decrease in the cytochrome oxidase activity. The method of fusion of liposomes with mitochondria developed by Hackenbrock [Hackenbrock and Chazotte (1986) Methods Enzymol. 125, 35-45] was employed in order to enrich the mitochondria cardiolipin content. We demonstrate that the lower cytochrome c oxidase activity in heart mitochondria from aged rats can be fully restored to the level of young control rats by exogenously added cardiolipin. No restoration was obtained with other phospholipids or with peroxidized cardiolipin. Our data support a key role for cardiolipin in the age-linked decline of rat heart mitochondrial cytochrome c oxidase activity.