Cardiolipin Remodeling in the Heart

Cardiolipin (CL) is a mitochondrial phospholipid that fundamentally contributes to the function of many proteins in the inner mitochondrial membrane, where it is actively involved in the integrity and flux of the electron transport chain. In the heart, functional CL is linoleic acid rich, and the loss of linoleic acid content is associated with cardiac disorders including ischemia and reperfusion, heart failure, and diabetes, as well as the X-linked recessive disease, Barth syndrome. To attain its high levels of linoleic acid, newly synthesized CL must initially undergo remodeling. CL modification and depletion by pathological processes may represent a failure of this remodeling pathway or activation of an alternative pathological remodeling pathway that causes the substitution of higher molecular weight, polyunsaturated fatty acyl side chains such as arachidonic or docosahexaenoic acid onto CL. This remodeling may occur in response to the alteration of CL by oxidative mechanisms, but the substituted side chains can also provoke further oxidation of CL. It is increasingly thought that cardiac pathology may result, at least partially, due to changes in CL resulting from the pathological remodeling process. Dietary interventions may restore CL to its linoleic acid-rich form and improve cardiac function by redirecting the remodeling process.