Mitochondrial Disorders and Diagnosis

Mitochondria generate cellular energy in the form of ATP (adenosine triphosphate) by the process of oxidative phosphorylation (OXPHOS) [1, 2, 3, 4]. Most cells contain hundreds of mitochondria. Human mitochondrial DNA (mtDNA) is much smaller, encoding 37 gene products (13 proteins, 2 rRNAs and 22 tRNAs) over 16,569 base pairs [5,6]. All its encoded proteins are directly involved in oxidative phosphorylation and include components of complex I (NADH dehydrogenase subunits ND1, ND2, ND3, ND4, ND4L, ND5, ND6), complex III (cytochrome b), complex IV (cytochrome oxidase subunits I, II and III) and complex V (mitochondrial ATPase subunits 6 and 8) [7]. All other human genes encoding mitochondrial proteins (total estimated at around 1,100 [8]) are transcribed in the nucleus, translated in the cytoplasm and their products imported into mitochondria. The interplay between organellar and nuclear genomes accounts for a large part of the diversity in mitochondrial pathologies.