The feasibility of cytoplasmic transfer has now been documented by the Newcastle group in the UK (53) and a variant of this approach has been used in the US to produce two healthy “transmitochondrial” rhesus monkeys carrying

undetectable mtDNA from their biological mother (54). I hope that this brief update on the pathogenesis and therapy of mitochondrial diseases conveys the fervor of research in mitochondrial medicine and the exciting realization that effective therapy is finally within our grasp for at least some of these devastating disorders. Abbreviations ADP, adenosine diphosphate; ATP, adenosine triphosphate; ANT, adenine nucleotide translocator; Inhibitors,research,lifescience,medical CACT, carnitine- acyl-carnitine translocase, CoQ, coenzyme Q; CPT, carnitine palmitoyltransferase; DIC, dicarboxylate carrier; ETF, electron-transfer flavoprotein; ETFDH, ETF dehydrogenase; FAD, flavin adenine dinucleotide; FADH2, reduced FAD; NADH, reduced nicotinamide adenine dinucleotide; PDHC, pyruvate Inhibitors,research,lifescience,medical dehydrogenase complex; TCA, tricarboxylic Inhibitors,research,lifescience,medical acid; I, complex I; II, complex II; III, complex III; IV, complex IV; V, complex V. Modified from 55 Acknowledgements Part of the work described here is supported by NIH grant HD32062 and by the Marriott Mitochondrial Disorder Clinical Research Fund (MMDCRF).
Lipid consists of two types of molecules:

fatty acid and its derivatives including triglycerides (TG), and sterol- containing metabolites such as cholesterol. Fatty acids Inhibitors,research,lifescience,medical are catabolized through β-oxidation cycle in mitochondrial matrix and thus ATP is CT99021 produced. Short- and medium- chain fatty acids can enter cells and then mitochondria by diffusion but long-chain fatty acids require fatty acid transporters at the plasma membrane and carnitine palmitoyltransferase (CPT) system at the mitochondrial membranes. Lipid dysmetabolism, Inhibitors,research,lifescience,medical involving intracellular TG catabolism, the transport of long-chain

fatty acids and carnitine, or β-oxidation, often causes different extent of lipid accumulation in skeletal muscle fibers and in other organs. Among the disorders of lipid metabolism, primary carnitine deficiency Dipeptidyl peptidase (PCD), multiple acyl-coenzyme A dehydrogenase deficiency (MADD) and neutral lipid storage disease with ichthyosis (NLSDI) or myopathy (NLSDM) usually show markedly increased lipid droplets in muscle fibers which are ordinarily termed lipid storage myopathy (LSM). On the other hand, lipid storage could be mild or even absent in the defects of intramitochondrial fatty acid transport and β-oxidation. The phenotype of lipid metabolism disorders is heterogeneous but can generally be divided into two major categories (1), especially in late onset patients.