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Table 3. Genes directly related to oxidative phosphorylation biogenesis that have been linked to disease.
OXPHOS ETC subunits
Complex I
Mitochondrial-encoded subunits: Mt-ND1, Mt-ND2, Mt-ND3, Mt-ND4, Mt-ND4L, Mt-ND5,Mt-ND6
Nuclear-encoded subunits: NDUFA1, NDUFA2, NDUFA9, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFB3,
NDUFB9, NDUFB10, NDUFB11, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS6, NDUFS7,
NDUFS8, NDUFV1, NDUFV2
Complex II
Nuclear-encoded subunits: SDHA, SDHB, SDHD
Complex III
Mitochondrial-encoded subunits: Mt-CYB
Nuclear-encoded subunits: CYC1, UBCRB, UQCRC2
Complex IV
Mitochondrial-encoded subunits: Mt-CO1, Mt-CO2, Mt-CO3
Nuclear-encoded subunits: COX41, COX412, NDUFA4
Complex V
Mitochondrial-encoded subunits: Mt-ATP6, Mt-ATP8
Nuclear-encoded subunits: ATP5A1, ATP5E
OXPHOS assembly factors
Complex I
Nuclear-encoded genes: ACAD9, FOXRED1, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6,
NUBPL, TIMMDC1, TIMEM126B
Complex II
Nuclear-encoded genes: SCHAF1
Complex III
Nuclear-encoded genes: BCSIL, LYRM7, TTC19, UQCC2
Complex IV
Nuclear-encoded genes: COA3, COA5, COA6, COA7, COX10, COX14, SCO1, SCO2, COX15, COX20, PET100,
APOFT1, SURF1, PET 117
Complex V
Nuclear-encoded genes: ATPAF2, TMEM70, USMG5
Replication/homeostasis, transcription,
translation
mtDNA replication/homeostasis
Nuclear-encoded genes: POLG, POLG2, DNA2, MGME1, RNASEH1, TFAM, TWNK
Nucleotide pools
Nuclear-encoded genes: ABAT, DGUOK, MPV17, RRM2B, SAMHD1, SUCLA2, SUCLG1, TK2, TYMP
Electron carriers
Nuclear-encoded genes: COQ2, COQ4, COQ5, COQ6, COQ7, COQ8A, COQ9, PDSS1, PDSS2, CYCS, HCCS
Mt-tRNA biogenesis
Mitochondrial-encoded genes: MT-TA, MT-TC, MT-TD, MT-TE, MT-TF, MT-TG, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2,
MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MT-TT, MT-TV, MT-TW, MT-TY,
Nuclear-encoded genes: GTPP3, MTFMT, NSUN3, PUS1, ORSL1, TRIT1, TRMT5, TRMU, TRNT1, MTO1
Mt-tRNA aminoacylation
Nuclear-encoded genes: AARS2, CARS2, DARS2, FARS2, GARS, HARS2, IARS2, KARS2, LARS2, MARS2, NARS2,
PARS2, RARS2, SARS2, TARS2, VARS2, WARS2, YARS2
mtRNA expression/processing
Nuclear-encoded genes: ELAC2, FASTKD2, HSD17810, LRPPRC, MRM2, MTPAP, PNPT1, TRMG10C
Mitochondrial ribosome biosynthesis
Mitochondrial-encoded genes: mt-RNR1
Nuclear-encoded genes: MRPL12, MRPL44, MRP57, MRPS16, MRPS22, MRPS23, MRPS34, ERAL1, MMPL3
Translation
Nuclear-encoded genes: C12orf65, GRM1, GFM2, RMD1, TSFM, TUFM, TAC

which power the production of ATP at Complex V. There are seven mtDNA-encoded subunits of Complex
I combined with seven nuclear-encoded subunits that are responsible for the catalytic activity of Complex
I. Each of these subunits has validated pathological variants causing disease [Tables 3 and 4]. The other
31 supernumerary subunits have roles that have not been completely elucidated. However, pathological
variants have been determined in 13 of these latter subunits, suggesting significant roles in Complex I