Introduction
The human mitochondrial genome is a 16.5-kb circular molecule
that is present at thousands of copies per cell in most tissues.
Mitochondrial DNA (mtDNA) is maternally inherited and, because it
encodes thirty-seven genes required for oxidative phosphorylation
(OXPHOS), is essential for normal development and sustained
function of cells and tissues throughout life [1]. Specifically, it encodes
thirteen core subunits of four of the five OXPHOS complexes, two
rRNA subunits of mitochondrial ribosomes, and twenty-two organelle-
specific tRNAs. Mutations in mtDNA can affect the expression or
function of individual OXPHOS subunits, if they occur in one of the
protein-encoding genes, or can globally affect the OXPHOS system, if
they occur in a tRNA, rRNA, or a non-coding control region for
transcription or replication of the genome (e.g. the D-loop region). To
date, hundreds of pathogenic mtDNA mutations have been identified
that cause maternally inherited diseases, which, as a class, display