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Sulaiman et al. J Transl Genet Genom 2020;4:159-87 I https://doi.org/10.20517/jtgg.2020.27 Page 161

A

B

Figure 1. A: mtDNA mutations affect transcription, translation, enzyme complex, biochemistry, and cellular phenotype at different levels.
These mutations may give rise to homoplasmy or heteroplasmy conditions, which can result in a disease or normal phenotype, known as
a phenotypic threshold effect; B: The energy production process via oxidative phosphorylation (OXPHOS) may also lead to the formation
of reactive oxygen species (ROS) in the electron transport chain. Oxidative stress conditions could further lead to the destruction of
macromolecules, such as lipids, proteins, and DNA. Modified from a previous publication [16]

37 genes encoding two rRNAs, 22 tRNAs, and 13 proteins subunits [12,13] . To date, there are about 1000-2000
mitochondrial proteins; however, only 600 of these proteins have determined functions. mtDNA is a
[14]
multicopy genome, ranging from just ~100 copies in sperm to > 100,000 copies in mature oocytes . The
mtDNA genomes can exist either in homoplasmy (all genomes have an identical mtDNA genotype) or
heteroplasmy (a combination of genomes with different mtDNA genotypes). These conditions can lead
to various diseases or a normal phenotype, known as the phenotypic threshold effect. The inheritance
of mtDNA is strictly maternal since mitochondrial endonuclease degrades the mtDNA within paternal
mitochondria after fertilization [1,7,15] .

There are five complexes in the OXPHOS system, namely complexes I (NADH ubiquinone oxidoreductase),
complex II (succinate ubiquinone oxidoreductase), complex III (ubiquinone-cytochrome c reductase),
complex IV (cytochrome c oxidase) and complex V (ATP synthase) which is important for energy
production [6,12] . Embedded in this system are two electron carriers, ubiquinone coenzyme Q and cytochrome
C, which serve as electron transporters important for energy production. Leakage of electrons from
complexes I and III in the electron transport chain (ETC) can lead to the formation of ROS and oxidative
[9]
stress conditions . Oxidative stress occurs where there is an imbalance between the production of ROS,
[9]
such as superoxide anion, H O and the antioxidant defense mechanism to remove these radical molecules .
2,
2
Uncontrolled oxidative stress may induce various dysfunctions within the mitochondria and cells, which
could then lead to disease development [Figure 1].