Cardiolipin
A unique phospholipid found almost exclusively in the inner mitochondrial membrane, essential for the proper structure and function of the electron transport chain. Cardiolipin deficiency (due to TAFAZZIN gene mutations) causes Barth syndrome. Elamipretide binds to and stabilises cardiolipin.
Technical Context
Cardiolipin (CL) is a unique diphosphatidylglycerol lipid with four fatty acid chains (predominantly linoleic acid in the heart — tetralinoleoyl-CL or CL 18:2₄). CL functions: organising ETC supercomplexes (complexes I+III+IV form a respirasome; CL molecules fill the interfaces between complexes, acting as molecular glue), stabilising cristae curvature (CL's conical shape promotes negative membrane curvature at cristae tips), anchoring cytochrome c to the IMM (CL-cytochrome c interaction is essential for electron transfer), regulating mitophagy (externalised CL on OMM signals damaged mitochondria for degradation), and modulating apoptosis (CL peroxidation → cytochrome c release). In Barth syndrome: TAFAZZIN deficiency → immature CL species (monolysocardiolipin accumulates, mature tetralinoleoyl-CL is deficient) → destabilised cristae → impaired ETC function → reduced ATP, increased ROS → cardiomyopathy, myopathy, neutropenia. Elamipretide binds mature and immature CL species, providing structural stabilisation even with abnormal CL composition.