Mitochondrial Disorders

Complex	Name	mtDNA-Encoded Subunits	Inhibitor	Clinical Associations
Complex I	NADH dehydrogenase (NADH:ubiquinone oxidoreductase)	7 subunits (ND1–ND6, ND4L) — most common site of mtDNA mutations	Rotenone	LHON, Leigh syndrome, MELAS
Complex II	Succinate dehydrogenase (SDH)	NONE — entirely nuclear-encoded (only complex with no mtDNA subunits)	Malonate	Paraganglioma/pheochromocytoma (SDHB/C/D germline mutations); Leigh syndrome (rare)
Complex III	Cytochrome bc1 (ubiquinol:cytochrome c oxidoreductase)	1 subunit (cytochrome b)	Antimycin A	Exercise intolerance, encephalomyopathy
Complex IV	Cytochrome c oxidase (COX)	3 subunits (COX I, II, III)	Cyanide, carbon monoxide	Leigh syndrome (SURF1), KSS, fatal infantile COX deficiency
Complex V	ATP synthase (F₀F₁ ATPase)	2 subunits (ATP6, ATP8)	Oligomycin	NARP, Leigh syndrome (MT-ATP6)

Gene	Inheritance	Complex/Enzyme	Notes
MT-ATP6	Maternal	Complex V	When heteroplasmy >90% in NARP mutation
SURF1	Autosomal recessive	Complex IV assembly factor	Most common nuclear cause; relatively homogeneous phenotype
NDUFS4, NDUFS7, NDUFS8	Autosomal recessive	Complex I subunits	Complex I deficiency is most common biochemical finding in Leigh
PDHA1	X-linked	Pyruvate dehydrogenase E1α	PDH deficiency; responds to ketogenic diet and thiamine
SUCLA2	Autosomal recessive	Succinyl-CoA ligase	mtDNA depletion; methylmalonic aciduria

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