Each mitochondrion also houses one or more copies of a genome known as the mitochondrial genome. The mitochondrial genome encodes 13 proteins of the electron transfer chain (31, 32) (Figure 5), which is where OXPHOS takes place and is the cell’s major generator of ATP. Specifically, it encodes at least one subunit of each of the complexes of the electron transfer chain except for complex II. The mitochondrial genome also encodes 22 tRNAs interspersed between each of the coding genes and two rRNAs (31, 32) (Figure 6). The genome also has one non-coding region, which is the site of interaction of the nuclear-encoded transcription and replication factors that transcribe and replicate this bacterial originating genome (33).

Whilst the mitochondrial genome does not encode all of the genes of the mitochondrion, the mitochondrion acts as the vehicle for the transmission, segregation and inheritance of the mitochondrial genome (21). Indeed, it has previously been argued that the key genes associated with the mitochondrial genome translocated to the nucleus millions of years ago (34). However, the genes present within the mitochondrial genome are also highly important to cellular function. It is well characterised that mutation of or deletion to these genes can cause severe metabolic defects that result in large scale multisystem diseases, such as Leber’s Hereditary Optic Neuropathy, Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Neuropathy, ataxia, and retinitis pigmentosa (NARP), Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome and Leigh Syndrome (reviewed in (22)). Furthermore, the presence of very high levels of deletion or mutation can also be fatal.