Kardiolipin

Cardiolipin, also known as diphosphatidylglycerol, is a phospholipid predominantly found in the inner mitochondrial membrane. It is structurally unique among phospholipids, consisting of two phosphatidylglycerol units linked by a glycerol backbone, giving it four fatty acyl chains and a net negative charge. This arrangement supports membrane curvature and helps organize protein complexes involved in energy metabolism.

Cardiolipin is synthesized in the mitochondrion from phosphatidylglycerol and CDP-diacylglycerol by cardiolipin synthase, and its acyl-chain composition is remodeled by enzymes such as tafazzin to produce tissue-specific species. Proper remodeling is essential for mitochondrial function; defects can lead to abnormal cardiolipin species and impaired respiration.

In mitochondria, cardiolipin plays a central role in oxidative phosphorylation by stabilizing respiratory chain supercomplexes and supporting the function of electron transport chain complexes and ATP synthase. It also participates in apoptosis and mitophagy; oxidation or externalization of cardiolipin on the inner membrane can promote cytochrome c release and signaling for cell death, while damaged mitochondria often present cardiolipin signals that recruit autophagic machinery. Cardiolipin interacts with several proteins and contributes to the maintenance of cristae structure.

Clinical and research relevance exists around disruptions of cardiolipin homeostasis. Barth syndrome, caused by mutations in the tafazzin gene, leads to abnormal cardiolipin remodeling and cardiomyopathy. Autoantibodies to cardiolipin are associated with antiphospholipid syndrome, which can cause thrombosis. Oxidized cardiolipin has been linked to aging and neurodegenerative processes, and cardiolipin exposure on damaged mitochondria can trigger mitophagy.