Table 1.

Mechanisms involved in mtDNA repair. The best characterised DNA repair pathway in mitochondria is the BER pathway. Several publications have investigated the role of the BER machinery in mtDNA maintenance and the difference to its nuclear counterpart. Attempts to elucidate the presence of other mtDNA repair mechanisms have been performed with contradictory results. Here, we enlist proteins known to be involved in different nuclear repair pathways and that have been studied for their role in mtDNA integrity and stability. Underlined text represents enzymes with exclusive mitochondrial localisation. DSBs = double-strand DNA breaks; HR = homologous recombination; LP-BER = long-patch base excision repair; MMR = mismatch repair; NHEJ = nonhomologous end joining; SSBs = single-strand DNA breaks.

Repair Pathway	Lesion	Enzyme	Enzyme Class	Function	Note	Ref.
BER	Oxidative damage	MUTHY AGG UNG	Hydrolase	Monofunctional glycosylase		[66]
		OGG1 NTH		Bifunctional glycosylase (β-elimination)
		NEIL1 NEIL2		Bifunctional glycosylase (βδ-elimination)
		APE1 PNK	Hydrolase	Hydrolysis of phosphate backbone		[67,68]
		Polγ	Transferase	Nucleotide incorporation		[69]
		FEN-1	Hydrolase	Cleavage of 5′ flap structures	LP-BER	[70]
		ExoG		Removal of 5′-blocking moiety	LP-BER	[71]
		DNA ligase III	Ligase	Nick ligation
MMR	Base mismatches	YB-1	DNA-binding protein	Mismatch sensing and protein recruitment		[39,72]
HR/NHEJ	SSBs and DSBs	No evidence of HR/NHEJ activity in mammalian mitochondria
mtDNA degradation	Any lesion	MGME1	Hydrolase	5’–3’ exonuclease activity	Involved in degradation of linear DNA after DSBs	[73]
		Twinkle	Helicase	Unwinding of mtDNA replication fork	Potentially involved in mtDNA degradation	[74,75]
		mtSSB	Single-strand DNA binding protein	Enhancing Twinkle and Polγ activity		[11,59]