Biochemistry · Enzyme
Complex I (NADH dehydrogenase) !
Complex I is NADH's entry door to the respiratory chain: it passes NADH's electrons to ubiquinone and pumps protons.
Updated 2026-11-01
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Key facts
- NADH + Q + 5 H⁺ (matrix) → NAD⁺ + QH₂ + 4 H⁺ (intermembrane space).
- It is the largest complex of the chain (about 45 subunits, 7 encoded by mitochondrial DNA) and L-shaped: one arm in the matrix, one in the membrane.
- Electrons travel from NADH to FMN and along a row of Fe-S clusters to ubiquinone.
- Rotenone and piericidin block the ubiquinone site.
- Also called
- NADH:ubiquinone oxidoreductase
- EC number
- 7.1.1.2
- Genes
- MT-ND1–MT-ND6, MT-ND4L, NDUFS1, NDUFS2, NDUFV1…
- Structure (PDB)
- 7VBZ
Regulation
- It depends on NADH supply and on respiratory control (available ADP).
- With excess ubiquinol and a high gradient it can run backwards and make a lot of superoxide.
Inhibitors and toxins
- Rotenone
- Piericidin A
- Amobarbital
- Metformin (weak effect, still debated)
Clinical notes
- Variants in MT-ND1, MT-ND4 and MT-ND6 cause Leber hereditary optic neuropathy.
- Complex I deficiency is the most common isolated respiratory chain defect and the most frequent cause of Leigh syndrome.
- Rotenone given to animals reproduces features of Parkinson disease; it is an experimental model.
Pathways
Related conditions
- Leber hereditary optic neuropathy (LHON)
- Leigh syndrome
- MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes)
- Lactic acidosis
Related
- NAD⁺ (nicotinamide adenine dinucleotide)
- Ubiquinone (coenzyme Q₁₀)
- Complex III (cytochrome bc₁)
- Succinate dehydrogenase (complex II)
- FAD (flavin adenine dinucleotide)
- Reactive oxygen species and antioxidants
Test yourself
Think of the answer, then tap the question to see it.
Which prosthetic group first receives NADH's electrons in complex I?
FMN, made from riboflavin (B2); from there they pass through Fe-S clusters to ubiquinone.
How many protons does complex I pump per NADH?
Four, from the matrix side into the intermembrane space.
Which classic complex I inhibitor is used as an insecticide?
Rotenone: it blocks the ubiquinone site.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: MT-ND1: NADH-ubiquinone oxidoreductase chain 1 (human) (UniProt, 2026); Complex I biogenesis (Reactome, 2026); MT-ND4 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 7VBZ: Matrix arm of active state CI from Rotenone-NADH dataset (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.