Mitochondrial dysfunction in heart failure: potential for therapeutic interventions?

See article by Jarreta et al. [4] (pages 860–865) in this issue. Cardiac work is supported by a high rate of ATP hydrolysis, matched by ATP production through mitochondrial oxidative phosphorylation (Fig. 1). Low ATP content in cardiac tissue was observed in patients with chronic heart failure despite the absence of myocardial ischaemia [1]. Mitochondrial function in cardiac tissue from the failing heart demonstrated that the capacity of the mitochondria for oxygen consumption and oxidative phosphorylation are significantly reduced compared to the normal heart [2]. Furthermore, morphological examination of the failing heart by electron microscopy revealed that the mitochondria are disrupted and damaged [3]. The paper by Jarreta et al. in this issue of Cardiovascular Research shows in both idiopathic dilated cardiomyopathy (IDC) and heart failure patients with a history of ischaemic coronary disease (IC) that the activity of complex III of the electron transport chain is reduced, without changes in the activities of complexes I, II or IV, or in the mitochondrial marker enzyme citrate synthase [4]. Evidence for a causal link between impaired mitochondrial metabolic function and cardiac failure was found in several cases of inherited cardiomyopathies [5], presenting as classic IDC. Surprisingly little is known about the molecular aspects of mitochondrial pathology in the failing heart. While point mutations in key mitochondrial enzymes could significantly impair the ability of the mitochondria to generate ATP, Jarreta et al. [4] found only neutral polymorphisms in the mitochondrial cytochrome b gene, suggesting that the complex III defect is not a primary mitochondrial disease.