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CONTACT USCardiolipin is a unique phospholipid that is found mainly in the inner mitochondrial membrane, accounting for about 20% of the total lipids. Among phospholipid species, cardiolipin has interesting chemical and structural characteristics, being highly acid and having a head group (glycerol) that is esterified to two phosphatidyl glyceride backbone fragments rather than one, resulting in a very specific ultrastructure and role in the mitochondrial function. In addition to acting as the signature phospholipid of mitochondria membranes, cardiolipin plays an important role in the bioenergetic processes of mitochondria, including the production of ATP. It interacts with a wide range of proteins, enzymes, and metabolite carriers, participating in a variety of reactions and helping to obtain optimal performance of various compounds.
Figure 1. The structure of cardiolipin.
Cardiolipin is present universally in both prokaryotes and eukaryotes where it represents an important phospholipid component of specific membranes in those organelles. It contains two phosphatidyl moieties joined by a central glycerol backbone, forming a dimeric structure. Thus, unlike other phospholipids that contain two fatty acyl chains linked by glycerol, cardiolipin has four acyl chains. Considering the potential number of combinations of fatty acyl groups, a very large number of cardiolipin species may be possible. Cardiolipin has three potential optically active carbons, two on the phosphatidyl groups and the third on the central carbon of the linking glycerol. Saturated chain cardiolipins form normal lamellar phase (the structure is can-shaped), while the more biologically relevant cardiolipins containing highly unsaturated chains prefer nonlamellar phases (the structure is a conical shape with a wider base than the head, see Figure 2B). Under biological conditions where cardiolipin is dispersed with other phospholipids (primarily phosphatidylcholines and phosphatidylethanolamines), the mixture prefers the lamellar (normal bilayer) phase.
Figure 2. Major characteristics of cardiolipin. (A) The chemical structure of cardiolipin is defined by its double glycerophosphate backbone and four fatty acyl chains (R1–R4). (B) The presence of a double glycerophosphate backbone and four fatty acyl side chains confers a conical shape to cardiolipin. (C) Cardiolipin present in a lipid bilayer induces a negative curvature. (D) Cardiolipin promotes the formation of highly curved regions within the inner mitochondrial membrane (IMM) [1].
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