Cardiolipin is a major membrane phospholipid in the mitochondria and is 
essential for cellular energy metabolism mediated through mitochondrial 
oxidative phosphorylation. Recent studies indicate that it plays a diverse role 
in cellular metabolism. Eukaryotic cardiolipin is synthesized de novo from 
phosphatidic acid via the cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol pathway 
and is deacylated to monolysocardiolipin in order for it to be remodelled into 
the form that is observed in mitochondrial membranes. This resynthesis of 
deacylated cardiolipin from monolysocardiolipin occurs via the Barth Syndrome 
gene product tafazzin and acyllysocardiolipin acyltransferase-1, 
monolysocardiolipin acyltransferase-1 and the alpha subunit of trifunctional 
protein. Heart failure is a disease condition in which the amount and type of 
cardiolipin is altered. Several animal models have been generated to study the 
role of altered cardiolipin in heart failure. In many of these models loss of 
the tetralinoleoyl-cardiolipin species is observed during the development of the 
heart failure. In the doxycycline inducible short hairpin RNA tafazzin knock 
down mouse, loss of tetralinoleoyl-cardiolipin is associated with a 
mitochondrial bioenergetic disruption. Reduction in mitochondrial supercomplex 
formation and NADH dehydrogenase activity within these supercomplexes is 
observed. Modulation of CL fatty acyl composition may serve as a therapeutic 
strategy for the treatment of several pathologies including cardiac 
dysfunction.We propose that increasing cardiolipin may improve mitochondrial 
function and potentially serve as a therapy for diseases which exhibit 
mitochondrial dysfunction involving reduced cardiolipin.