Cardiolipin

Cardiolipin is a phospholipid that is enriched in the inner mitochondrial membrane of most eukaryotes and is also present in bacterial membranes. Its molecule consists of two phosphatidyl groups linked by a glycerol backbone, giving four fatty acyl chains and two phosphate groups. This tetra-acyl diphosphatidylglycerol structure makes cardiolipin highly unique among phospholipids.

In mitochondria, cardiolipin supports the organization and function of the respiratory chain by stabilizing protein complexes and assisting the formation of supercomplexes. Its anionic head groups and distinctive acyl composition promote interactions with several electron transport chain proteins and contribute to the maintenance of membrane curvature and integrity.

Cardiolipin is synthesized in mitochondria by cardiolipin synthase from phosphatidylglycerol and CDP-diacylglycerol, with the product cardiolipin subsequently remodeled by acyl-chain remodeling enzymes such as tafazzin to yield mature species. This remodeling creates tissue-specific cardiolipin profiles that influence function.

Cardiolipin participates in apoptosis signaling; oxidation and translocation of cardiolipin can facilitate the release of cytochrome c from mitochondria and amplify pro-apoptotic pathways. In addition, cardiolipin oxidation is implicated in aging and various neurodegenerative and cardiovascular diseases.

Clinically, abnormalities in cardiolipin metabolism are linked to Barth syndrome, a genetic disorder caused by mutations in tafazzin, and to changes observed in heart failure and some neurodegenerative disorders. Cardiolipin content and composition also respond to oxidative stress and aging.

Methods to study cardiolipin include mass spectrometry for lipid profiling and fluorescent probes such as 10-nonyl acridine orange for visualization in mitochondria.