Cardiolipin Metabolism and the Role it Plays in Heart Failure and Mitochondrial Supercomplex Formation
Edgard M. Mejia, Laura K. Cole and Grant M. Hatch
Affiliation: Department of Pharmacology & Therapeutics, University of Manitoba, Manitoba Institute of Child Health, 501C-715 McDermot Avenue, Winnipeg, Manitoba, Canada, R3E 3P4.
Keywords: Barth syndrome, cardiolipin, heart failure, mitochondria, monolysocardiolipinacyltransferase, phospholipid,
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.
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