Cardiolipin is a unique
phospholipid which is almost exclusively located at the level of the inner mitochondrial membrane where it is biosynthesized. This
phospholipid is known to be intimately involved in several mitochondrial bioenergetic processes. In addition,
cardiolipin also has active roles in several of the mitochondrial-dependent steps of apoptosis and in mitochondrial membrane dynamics. Alterations in
cardiolipin structure, content and acyl chains composition have been associated with
mitochondrial dysfunction in multiple tissues in several physiopathological conditions, including
ischemia/reperfusion, different thyroid states, diabetes, aging and
heart failure.
Cardiolipin is particularly susceptible to ROS attack due to its high content of
unsaturated fatty acids. Oxidative damage to
cardiolipin would negatively impact the biochemical function of the mitochondrial membranes altering membrane fluidity, ion permeability, structure and function of components of the mitochondrial electron transport chain, resulting in reduced mitochondrial oxidative phosphorylation efficiency and apoptosis. Diseases in which
mitochondrial dysfunction has been linked to
cardiolipin peroxidation are described. Ca(2+), particularly at high concentrations, appears to have several negative effects on mitochondrial function, some of these effects being linked to CL peroxidation.
Cardiolipin peroxidation has been shown to participate, together with Ca(2+), in mitochondrial permeability transition. In this review, we provide an overview of the role of CL peroxidation and Ca(2+) in
mitochondrial dysfunction and disease.