Abstract
Cardiolipin is a signature phospholipid of major functional significance in mitochondria. In heart mitochondria the fatty acid composition of cardiolipin is commonly viewed as highly regulated due to its high levels of linoleic acid (18:2n − 6) and the dominant presence of a 4×18:2 molecular species. However, analysis of data from a comprehensive compilation of studies reporting changes in fatty acid composition of cardiolipin in heart and liver mitochondria in response to dietary fat shows that, in heart the accrual of 18:2 into cardiolipin conforms strongly to its dietary availability at up to 20% of total dietary fatty acid and thereafter is regulated. In liver, no dietary conformer trend is apparent for 18:2 with regulated lower levels across the dietary range for 18:2. When 18:2 and docosahexaenoic acid (22:6n − 3) are present in the same diet, 22:6 is incorporated into cardiolipin of heart and liver at the expense of 18:2 when 22:6 is up to ~20% and 10% of total dietary fatty acid respectively. Changes in fatty acid composition in response to dietary fat are also compared for the two other main mitochondrial phospholipids, phosphatidylcholine and phosphatidylethanolamine, and the potential consequences of replacement of 18:2 with 22:6 in cardiolipin are discussed.
Highlights
Cardiolipin (CL) is the only prevalent di-phospholipid present in mammalian membranes [1–4] and is primarily found in the inner leaflet of the inner mitochondrial membrane where it is synthesized [1].As a consequence of its structure CL possesses four rather than the usual two fatty acids and may be viewed either as two phosphatidic acid molecules joined together by glycerol, or as a phosphatidic acid joined to a phosphatidylglycerol molecule, or even as two phosphatidylglycerol molecules sharing the same glycerol molecule
As mitochondria membranes represent a significant portion of cell phospholipids and CL, PC and PE are the most common mitochondrial phospholipids, increases in their 22:6 content presumably accounts for a portion of the well-known [50] dietary induced increase in 22:6 levels in total membrane phospholipids
The best-known CL molecular species is the tetra-linoleic (4×18:2) species that dominates in mammalian heart mitochondria
Summary
Cardiolipin (CL) is the only prevalent di-phospholipid present in mammalian membranes [1–4] and is primarily found in the inner leaflet of the inner mitochondrial membrane where it is synthesized [1]. Phospholipids vary extensively in their acyl composition containing a mixture of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids [8], yet most phospholipids (>99%) in mammalian membranes avoid multiple PUFAs on the same phospholipid molecule [8,9] This seems not to apply to CL that in cardiac mitochondria has a high PUFA content with a tetra-linoleic acid (4×18:2n − 6) molecular species being its most prevalent molecule. Unusual as one of the widely held beliefs about mammalian CL fatty acid composition is that it is highly regulated, primarily due to its high levels of 18:2 and the prevalence of a 4×18:2 molecular species in cardiac mitochondria and an apparent resistant to dietary manipulation [12]. We review the evidence that, contrary to popular belief, CLs PUFA composition is amenable to change dependent upon the fat composition of the diet, the presence of docosahexaenoic acid (22:6n − 3) that will readily replace 18:2 when present in the diet at up to 20% of total fatty acid
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