Decreased cardiolipin synthesis corresponds with cytochrome c release in palmitate-induced cardiomyocyte apoptosis

Apoptosis has been identified recently as a component of many cardiac patho logies. However, the potential triggers of programmed cell death in the hea rt and the involvement of specific metabolic pathway(s) are less well chara cterized. Detachment of cytochrome c from the mitochondrial inner membrane is a necessary first step for cytochrome c release into the cytosol and ini tiation of apoptosis. The saturated long chain fatty acid, palmitate, induc es apoptosis in rat neonatal cardiomyocytes and diminishes content of the m itochondrial anionic phospholipid, cardiolipin. These changes are accompani ed by 1) acyl chain saturation of phosphatidic acid and phosphatidylglycero l, 2) large increases in the levels of these two phospholipids, and 3) a de cline in cardiolipin synthesis. Although cardiolipin synthase activity is u nchanged, saturated phosphatidylglycerol is a poor substrate for this enzym e. Under these conditions, decreased cardiolipin synthesis and release of c ytochrome c are directly and significantly correlated. The results suggest that phosphatidylglycerol saturation and subsequent decreases in cardiolipi n affect the association of cytochrome c with the inner mitochondrial membr ane, directly influencing the pathway to cytochrome c release and subsequen t apoptosis.