1. Introduction other sources, eg glycolytic metabolism is limited in normal cardiac tissue. Fatty acid ß-oxidation and the The heart is highly dependent for its function on oxidationofcarbohydratesthroughtheTCAcyclegenerate oxidative energy generated in mitochondria, primarily by the majority of intramitochondrial NADH and FADH fatty acid ß-oxidation, respiratory electron chain and which are the direct source of electrons for the electron oxidative phosphorylation (OXPHOS). In this review, we transport chain (and produce as well a small proportion of survey the available evidence that mitochondrial dysfunc- the ATP supply)(Fig. 1)[1]. The heart also maintains tion may play a pivotal role in cardiac failure. We also stored high-energy phosphates (eg ATP and phosphodiscuss how mitochondrial dysfunction may be related to creatine pools). other critical cellular and molecular changes found in Myocyte ATP is needed and utilized by actomyosin cardiac hypertrophy and failure, including dysfunctional ATPase and various ion pumps during contraction and structural and cytoskeletal proteins, apoptosis, calcium flux relaxation in cardiac cells. Moreover, decreased cellular and handling, and signalling pathways. The review also ATP levels (due to mitochondrial dysfunction) can markfocuses on the biochemical and molecular changes in edly lower the threshold of plasma membrane depolarizasevere heart failure secondary to primary cardiomyopathy tion [2] and therefore potentially influence impulse gene-(dilated/hypertrophic) in humans as well as findings in ration and conduction in the myocardium. animal models of heart failure related to volume and/or pressure overload.