Table 1: Genes involved in the biogenesis or maintenance of multiple OXPHOS complexes and implicated in mitochondrial disorders.

Affected processGeneProtein (function)References

Combined OXPHOS deficiencies with normal complex II activities a
MtDNA replicationPOLGPolymerase 𝛾 catalytic subunit[13, 213]
POLG2Polymerase 𝛾 accessory subunit[13, 214]
C10orf2Twinkle (mtDNA helicase)[13]

Nucleotide synthesis and transportDGUOKDeoxyguanosine kinase[13]
TK2Thymidine kinase 2[13]
TYMPEndothelial cell growth factor 1 (thymidine phosphorylase)[13]
SLC25A4Adenine nucleotide translocator 1[13]
SLC25A3Solute carrier family 25 member 3 (phosphate transporter)[43, 215] c
SUCLG1Succinate-CoA ligase 𝛼 -subunit[43, 216]
SUCLA2Succinate-CoA ligase 𝛽 -subunit[13, 216]
RRM2BRibonucleotide reductase M2 B[13, 217]
MPV17Mt inner membrane protein[13]

Mt translation22 mitochondrial tRNA genes[12]
2 mitochondrial rRNA genes[12]
GFM1Mt translation elongation factor G1[15]
TSFMMt translation elongation factor Ts[21]
TUFMMt translation elongation factor Tu[22]
MRPS16Mt ribosomal protein S16[18]
MRPS22Mt ribosomal protein S22[19]
PUS1Pseudouridine synthase 1[14]
TRMUtRNA 5-methylaminomethyl-2-thiouridylate methyltransferase[24]
DARS2Mt aspartyl-tRNA synthetase 2[20] c
RARS2Mt arginyl-tRNA synthetase 2[16]

Other combined OXPHOS deficiencies b
Mt protein importTIMM8ATranslocase of inner mt membrane 8 homolog A (small TIM complex subunit)[74] c
DNAJC19DnaJ homolog, subfamily C, member 19 (TIM23 complex subunit)[76]

Mt membrane biogenesis and maintenanceTAZTafazzin (cardiolipin metabolism)[203, 218]
OPA1Optic atrophy 1 (mt fusion)[205]
MFN2Mitofusin 2 (mt fusion)[205]
DNM1LDynamin 1-like (mt and peroxisomal fission)[207] c

Mt protein processing and quality controlSPG7Spastic paraplegia 7 or paraplegin (m-AAA protease subunit)[144, 219]

a Based 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.
b All 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.
c The OXPHOS complexes showed normal activities.