Carnitine and carnitine esters in mitochondrial metabolism and function

Under physiological conditions, myocardial energy production is almost entirely dependent on mitochondrial oxidative phosphorylation [1]. At rest, in the post-absorptive state, the major fuel for mitochondrial oxidation is represented by long-chain fatty acids [2]. The degradation of these substrates occurs in mitochondria and carnitine is required for the transport of activated acyls, namely acyl-CoAs, across the inner mitochondrial membrane [3, 4]. The alteration of this process may result in cytosolic accumulation of triglycerides leading eventually to heart failure [5, 6]. Thus, it is hardly surprising that cardiologists focused their attention on carnitine, linking this factor exclusively to lipid metabolism. However, by its interaction with coenzyme A (CoA), carnitine exerts a role in any CoA-dependent process [7–9]. The modulation of the ratio between free CoA (CoASH) and esterified CoA can be seen as the main task accomplished by carnitine. An increase in CoASH availability or a decrease in acyl-CoA levels expands the roles of carnitine to substrate choice [10], removal of inhibitory metabolites [11] or modulation of key enzymatic steps [7, 9, 12, 13]. In addition, some carnitine esters appear to specifically modify cell metabolism and function [7, 14].