Cardiolipin is a unique phospholipid which is almost exclusively located in the inner mitochondrial membrane where it is biosynthesized. Considerable progress has recently been made in understanding the role of cardiolipin in mitochondrial function and bioenergetics. This phospholipid is associated with membranes designed to generate an electrochemical gradient that is used to produce ATP, such as bacterial plasma membranes and inner mitochondrial membrane. This ubiquitous and intimate association between cardiolipin and energy transducing membranes indicates an important role for cardiolipin in mitochondrial bioenergetic processes. Cardiolipin has been shown to interact with a number of proteins, including the respiratory chain complexes and substrate carrier proteins. Over the past decade, the significance of cardiolipin in the organization of components of the electron transport chain into higher order assemblies, termed respiratory supercomplexes, has been established. Moreover, cardiolipin is involved in different stages of the mitochondrial apoptotic process, as well as in mitochondrial membrane stability and dynamics. This review discusses the current understanding of the functional role that cardiolipin plays in several reactions and processes involved in mitochondrial bioenergetics. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components.

Reactive oxygen species (ROS) are considered a key factor in mitochondrial dysfunction associated with brain aging process. Mitochondrial respiration is an important source of ROS and hence a potential contributor to brain functional changes with aging. In this study, we examined the effect of aging on cytochrome c oxidase activity and other bioenergetic processes such as oxygen consumption, membrane potential and ROS production in rat brain mitochondria. We found a significant age-dependent decline in the cytochrome c oxidase activity which was associated with parallel changes in state 3 respiration, membrane potential and with an increase in H2O2 generation. The cytochrome aa3 content was practically unchanged in mitochondria from young and aged animals. The age-dependent decline of cytochrome c oxidase activity could be restored, in situ, to the level of young animals, by exogenously added cardiolipin. In addition, exposure of brain mitochondria to peroxidized cardiolipin resulted in an inactivation of this enzyme complex. It is suggested that oxidation/depletion of cardiolipin could be responsible, at least in part, for the decline of cytochrome c oxidase and mitochondrial dysfunction in brain aging. Melatonin treatment of old animals largely prevented the age-associated alterations of mitochondrial bioenergetic parameters. These results may prove useful in elucidating the molecular mechanisms underlying mitochondrial dysfunction associated with brain aging process, and may have implications in etiopathology of age-associated neurodegenerative disorders and in the development of potential treatment strategies.