Cardiolipin (IUPAC name 1,3-bis(sn-3’-phosphatidyl)-sn-glycerol, "sn" designating stereospecific numbering) is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition.

[4] It has been proposed that the (18:2)4 acyl chain configuration is an important structural requirement for the high affinity of CL to inner membrane proteins in mammalian mitochondria.

[5] However, studies with isolated enzyme preparations indicate that its importance may vary depending on the protein examined.

[citation needed] In vitro experiments have shown that CL has high affinity for curved membrane regions.

Based on this special structure, the fluorescent mitochondrial indicator, nonyl acridine orange (NAO) was introduced in 1982,[7] and was later found to target mitochondria by binding to CL.

The detection, quantification, and localisation of CL species is a valuable tool to investigate mitochondrial dysfunction and the pathophysiological mechanisms underpinning several human disorders.

[2][3][14] In prokaryotes such as bacteria, diphosphatidylglycerol synthase catalyses a transfer of the phosphatidyl moiety of one phosphatidylglycerol to the free 3'-hydroxyl group of another, with the elimination of one molecule of glycerol, via the action of an enzyme related to phospholipase D. The enzyme can operate in reverse under some physiological conditions to remove cardiolipin.

Catabolism of cardiolipin may happen by the catalysis of phospholipase A2 (PLA) to remove fatty acyl groups.

Complex IV has been shown to require two associated CL molecules in order to maintain its full enzymatic function.

Cytochrome bc1 (Complex III) also needs cardiolipin to maintain its quaternary structure and functional role.

[17] Complex V of the oxidative phosphorylation machinery also displays high binding affinity for CL, binding four molecules of CL per molecule of complex V.[18] Cardiolipin distribution to the outer mitochondrial membrane would lead to apoptosis of the cells, as evidenced by cytochrome c (cyt c) release, Caspase-8 activation, MOMP induction and NLRP3 inflammasome activation.

Thus, this bicyclic structure can serve as an electron buffer pool to release or absorb protons to maintain the pH near the membranes.

As the number of human diseases with CL profile abnormalities has exponentially grown, the use of qualitative and quantitative diagnostics has emerged as a necessity.

Tafazzin is an indispensable enzyme to synthesize cardiolipin in eukaryotes involved in the remodeling of CL acyl chains by transferring linoleic acid from PC to monolysocardiolipin.

In the metabolic disease combined malonic and methylmalonic aciduria (CMAMMA) due to ACSF3 deficiency, there is an altered composition of complex lipids as a result of impaired mitochondrial fatty acid synthesis (mtFAS), so for example the content of cardiolipins is strongly increased.

[31] It is also associated with a 15% reduction in linked complex I/III activity of the electron transport chain, which is thought to be a critical factor in the development of Parkinson's disease.

[32] Recently, it is reported that in non-alcoholic fatty liver disease[33] and heart failure,[34] decreased CL levels and change in acyl chain composition are also observed in the mitochondrial dysfunction.

Anti-cardiolipin antibodies can also be increased in numerous other conditions, including systemic lupus erythematosus, malaria and tuberculosis, so this test is not specific.

Patients with anti-cardiolipin antibodies (Antiphospholipid syndrome) can have recurrent thrombotic events even early in their mid- to late-teen years.

[39] Chronic fatigue syndrome is debilitating illness of unknown cause that often follows an acute viral infection.