Cardiolipin acyl composition is uniquely regulated and critically influences mitochondrial function

t is commonly hypothesized that membrane polyunsaturated fatty acids (PUFA) influence cell function through such general and non-specific phenomena as membrane peroxidation or fluidity. However, there is little evidence to suggest that oxidized fatty acids are present in the membranes of live cells or that fluidity measurements assess any true physiological function. Many studies demonstrate that oxidation of intact biological membranes occurs only upon the addition of artificial oxidants. These studies led this author to investigate live cells for a specific and demonstrable influence of membrane fatty acids on cell function.;A cell culture system was developed in which individual fatty acids were enriched into human colonic endothelial cells (HT-29) and the resulting changes in cell fatty acid composition determined. The fatty acid composition of the inner-mitochondrial membrane phospholipid, cardiolipin (CL), was of particular interest to this author for two reasons. First, CL acyl composition was extraordinarily changeable and could selectively and rapidly incorporate fatty acids with a wide range of physical structures. Second, CL is a critical structural component of the inner-mitochondrial membrane. Most enzymes involved in energy metabolism are dependent on an association with CL for activity. Because CL is both a critical and a changeable phospholipid pool, this author focused on determining the effects of CL acyl composition on mitochondrial function.;Live HT-29 cells enriched with oleic, linoleic, arachidonic, eicosapentaenoic or docosahexaenoic acids had mitochondrial potentials that were changed...