Acknowledgement We would like to thank Manuela Papacci for her helpful and precious assistance. Our research described in this paper was supported by grants from The Myositis Association, USA, Fondazione Don Gnocchi Onlus, UniversitàCattolica del SacroCuore, Roma.
Mitochondrial Respiratory Chain Disorders (MRCD) are a heterogeneous group of disorders that share the involvement

of the C59 in vitro cellular bioenergetic machinery due to molecular defects affecting the mitochondrial oxidative phosphorylation system (OXPHOS). Clinically, they usually involve multiple tissues although they tend to mainly affect nervous system and skeletal muscle. Cardiological manifestations are frequent Inhibitors,research,lifescience,medical and include hypertrophic or dilated cardiomyopathies and heart conduction defects, being part of adult or infantile multisystemic mitochondrial disorders Inhibitors,research,lifescience,medical or, less frequently, presenting as isolated clinical condition. The aim of this review is to update the cardiological manifestations in both adult and infantile mitochondrial disorders going briefly over mitochondrial genetics. Cardiac involvement is a common

feature associated with early and late onset forms of MRCD. Inhibitors,research,lifescience,medical In particular cases, these conditions should be considered into the diagnostic algorithm of idiopathic cardiomyopathies. Physicians strictly related with this disorders need to be aware of heart complications and therefore periodical cardiological examinations should be performed in such patients. Finally, therapeutic strategies are suggested to treat cardiac disorders in MRCD Key words: Mitochondrial cardiomyopathies, molecular diagnosis, therapy Introduction The mitochondria are complex organelles

responsible Inhibitors,research,lifescience,medical for many essential functions of the cellular machinery. They are primarily involved in the production of energy, assembling ATP molecules that are the final product of the respiratory chain (1). However, mitochondria also have an important role in apoptosis through the activation of the caspases cascade (2, Inhibitors,research,lifescience,medical 3), thus participating to neurodegenerative processes (4,5). Other mitochondrial functions include heat production (6) and the transmission Electron transport chain of maternal genetic traits (7, 8). The respiratory chain is composed of five enzymatic multimeric complexes (I, II, III, IV and V), embedded in the inner mitochondrial membrane. In addition, coenzyme Q (a lipoidal quinone) and cytochrome c are involved in mitochondrial respiration, serving as ‘electron shuttles’ between the complexes (9, 10). Most of the cellular energy is produced by mitochondria making them a target for the development of bioenergetic tissues deficits. Mitochondrial respiratory chain disorders (MRCD) are caused by sporadic or inherited mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Mitochondria are the only cellular organelles that possess their own genetic material, but their functions are crucially dependent on a wide array of proteins encoded by nuclear genes.