Table 1.

Diseases caused by mutations of the proteins regulating mtDNA replication.

Gene	Function	Disease	References
POLG	POLγ catalytic subunit	MIRAS, Parkinsonism, AHS, MCHS, MEMSA, ANS, ad/ar PEO, male infertility, testicular cancer	[47,51]
POLG2	POLγ accessory subunit	adPEO	[52]
TWINKLE	mtDNA helicase	PEO, hepatopathy, spinocerebellar ataxia, epileptic encephalopathy	[49]
RNASE H1	Endoribonuclease of the RNA-DNA hybrid	CPEO, exercise intolerance	[53]
SSBP1	Subunit of ssDNA-binding complex	optic atrophy	[50]
MGME1	Metal dependent ssDNA exonuclease	recessive multi-systemic mitochondrial disorder	[54]
TOP3A	Topoisomerase	CPEO plus syndrome	[55]
TFAM	Transcription factor	neonatal failure	[56]

Abbreviations: MIRAS, Mitochondrial recessive ataxia syndrome; AHS, Alpers–Huttenlocher syndrome; MCHS, myocerebrohepatopathy spectrum; MEMSA, myopathy sensory ataxia; ANS, ataxia neuropathy spectrum; CPEO, chronic progressive external ophthalmoplegia.