Cardiolipin

Cardiolipin (CL) is a special double phospholipid. It is found almost only in the inner membrane of your mitochondria. It makes up roughly 15 to 20% of that membrane's lipid. Its four fatty-acid tails are mostly linoleic acid in a healthy heart and muscle, forming 'tetra-linoleoyl cardiolipin' (TLCL). Those tails do two key jobs. They create the curve the membrane needs for its folds (cristae). And they act as molecular glue that holds the respiratory supercomplexes (complexes I, III, IV) together (Corey et al., 2022). Damage hits this hard. When ROS oxidize cardiolipin, the curvature breaks. The supercomplexes destabilize. And a protein called cytochrome c turns into a cardiolipin-attacking enzyme. The oxidized cardiolipin then lets go of the membrane. That releases cytochrome c into the cell, which triggers apoptosis (Kagan et al., 2005). With age, total cardiolipin and the TLCL form decline in heart, liver, brain, and muscle mitochondria in animal studies. Meanwhile, oxidized forms rise. In aged rat hearts, a loss of blood flow produces about 3 to 4 times more of one oxidized cardiolipin than in adult hearts (with no change in total cardiolipin; Lesnefsky and Hoppel, 2008). The evidence is still mostly experimental, from rodent, fish, and primate models. Human data are sparse and mostly associational (Yoo et al., 2025). One approved drug targets cardiolipin: elamipretide (SS-31, Forzinity). It got FDA accelerated approval for Barth syndrome (a genetic cardiolipin-remodeling disorder) in September 2025. Trials in heart failure and mitochondrial myopathy are ongoing.

Last reviewed: June 22, 2026

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