Functional role of cardiolipin in mitochondrial bioenergetics

Abstract

Cardiolipin is a unique phospholipid which is almost exclusively located in the inner mitochondrial membrane where it is biosynthesized. Considerable progress has recently been made in understanding the role of cardiolipin in mitochondrial function and bioenergetics. This phospholipid is associated with membranes designed to generate an electrochemical gradient that is used to produce ATP, such as bacterial plasma membranes and inner mitochondrial membrane. This ubiquitous and intimate association between cardiolipin and energy transducing membranes indicates an important role for cardiolipin in mitochondrial bioenergetic processes. Cardiolipin has been shown to interact with a number of proteins, including the respiratory chain complexes and substrate carrier proteins. Over the past decade, the significance of cardiolipin in the organization of components of the electron transport chain into higher order assemblies, termed respiratory supercomplexes, has been established. Moreover, cardiolipin is involved in different stages of the mitochondrial apoptotic process, as well as in mitochondrial membrane stability and dynamics. This review discusses the current understanding of the functional role that cardiolipin plays in several reactions and processes involved in mitochondrial bioenergetics. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components.

The phospholipid code: a key component of dying cell recognition, tumor progression and host–microbe interactions

“…129,130 Besides phosphatidylinositols, levels of the mitochondrial glycerophospholipid, cardiolipin, are also tightly controlled. Cardiolipin is abundant in the inner mitochondrial membrane where it acts as a key component of the electron transport chain, as well as having an essential role in the initiation of apoptosis through association with cytochrome C. 131 To coordinate these essential mitochondrial processes, cardiolipin synthase as well as a range of phospholipases exquisitely maintain cardiolipin levels within the mitochondria. 132 Another key mechanism in regulating the availability of phospholipids at different locations, particularly on which surface of the phospholipid bilayer, is mediated by nonspecific and specific lipid transporters.…”

Myostatin deficiency is associated with lipidomic abnormalities in skeletal muscles

“…rely on glycolytic metabolism to a greater extent than unaffected, age-matched controls, likely due to an impairment in fat oxidation. These findings highlight the crucial role that mitochondrial CL plays in skeletal muscle oxidative metabolism and mitochondria bioenergetics processes [26].…”

“…Actually, this specific phospholipid of the mitochondria plays an important role in respiratory chain (biogenesis, stability and activity of the respiratory complexes), in the β-oxidation of fatty acids and is involved in the last step of energy conversion, namely the production of ATP [24][25][26]. Crystallographic and nuclear magnetic resonance studies showed the presence of CL, in…”

“…Nascent CL is deactyled by CL deacylases/phospholipases to monolyso-CL which is reactylated principally by the taffazin to mature CL [19,25]. CL interacts with a number of inner mitochondrial membrane proteins, enzymes and metabolite carriers, such as the electron transport chain complexes involved in oxidative phosphorylation and ADP/ATP carriers, which optimize efficient electron/proton flux and hence, ATP synthesis [26]. CL is also involved in the β-oxidation of fatty acids, as a reduction of mature CL impairs skeletal muscle FA oxidation [27,28] and a positive correlation has been demonstrated between mitochondrial COX activity and CL content [29].…”

Cardiolipin puts the seal on ATP synthase

“…CL is now recognized as a prerequisite for optimal activity of respiratory chain proteins, including complex I (NADH/quinone oxidoreductase), complex III (cytochrome bc 1 ), complex IV (cytochrome c oxidase), and complex V (ATP synthase). A number of possible functions have been proposed for CL in OxPhos, ranging from protein rigidification to proton transfer (8). CL-protein interactions in the inner mitochondrial membrane are not limited to the OxPhos complexes, as witnessed by a rapidly growing list of other proteins interacting specifically with CL, ranging from ADP/ATP carriers to translocases (9,10).…”