Mitochondrial Translation and Beyond: Processes Implicated in Combined Oxidative Phosphorylation Deficiencies

Table 1

Genes involved in the biogenesis or maintenance of multiple OXPHOS complexes and implicated in mitochondrial disorders.

Affected process	Gene	Protein (function)	References
Combined OXPHOS deficiencies with normal complex II activities a
MtDNA replication	POLG	Polymerase 𝛾 catalytic subunit	[13, 213]
	POLG2	Polymerase 𝛾 accessory subunit	[13, 214]
	C10orf2	Twinkle (mtDNA helicase)	[13]
Nucleotide synthesis and transport	DGUOK	Deoxyguanosine kinase	[13]
	TK2	Thymidine kinase 2	[13]
	TYMP	Endothelial cell growth factor 1 (thymidine phosphorylase)	[13]
	SLC25A4	Adenine nucleotide translocator 1	[13]
	SLC25A3	Solute carrier family 25 member 3 (phosphate transporter)	[43, 215] c
	SUCLG1	Succinate-CoA ligase 𝛼 -subunit	[43, 216]
	SUCLA2	Succinate-CoA ligase 𝛽-subunit	[13, 216]
	RRM2B	Ribonucleotide reductase M2 B	[13, 217]
	MPV17	Mt inner membrane protein	[13]
Mt translation	22 mitochondrial tRNA genes		[12]
	2 mitochondrial rRNA genes		[12]
	GFM1	Mt translation elongation factor G1	[15]
	TSFM	Mt translation elongation factor Ts	[21]
	TUFM	Mt translation elongation factor Tu	[22]
	MRPS16	Mt ribosomal protein S16	[18]
	MRPS22	Mt ribosomal protein S22	[19]
	PUS1	Pseudouridine synthase 1	[14]
	TRMU	tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase	[24]
	DARS2	Mt aspartyl-tRNA synthetase 2	[20]^c
	RARS2	Mt arginyl-tRNA synthetase 2	[16]
Other combined OXPHOS deficiencies b
Mt protein import	TIMM8A	Translocase of inner mt membrane 8 homolog A (small TIM complex subunit)	[74] c
	DNAJC19	DnaJ homolog, subfamily C, member 19 (TIM23 complex subunit)	[76]
Mt membrane biogenesis and maintenance	TAZ	Tafazzin (cardiolipin metabolism)	[203, 218]
	OPA1	Optic atrophy 1 (mt fusion)	[205]
	MFN2	Mitofusin 2 (mt fusion)	[205]
	DNM1L	Dynamin 1-like (mt and peroxisomal fission)	[207] c
Mt protein processing and quality control	SPG7	Spastic paraplegia 7 or paraplegin (m-AAA protease subunit)	[144, 219]

aBased on the function of the affected proteins, a combined complex I, III, IV and V deficiency would be expected, however, not always do all these enzyme complexes display decreased activities.
bAll OXPHOS complexes are expected to malfunction based on the function of the affected proteins; nonetheless, large variations have been found in the exact OXPHOS complexes involved.
cThe OXPHOS complexes showed normal activities.