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[Biochemistry](https://durgical.com/en/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](https://www.enzyme-database.org/query.php?ec=7.1.1.2)

**Genes**
MT-ND1–MT-ND6, MT-ND4L, NDUFS1, NDUFS2, NDUFV1…

**Structure (PDB)**
[7VBZ](https://www.rcsb.org/structure/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

- [Electron transport chain and oxidative phosphorylation](https://durgical.com/en/biochemistry/pathways/electron-transport-chain-and-oxidative-phosphorylation/)

## Related conditions

- [Leber hereditary optic neuropathy (LHON)](https://durgical.com/en/conditions/leber-hereditary-optic-neuropathy/)
- [Leigh syndrome](https://durgical.com/en/conditions/leigh-syndrome/)
- [MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes)](https://durgical.com/en/conditions/melas/)
- [Lactic acidosis](https://durgical.com/en/conditions/lactic-acidosis/)

## Related

- [NAD⁺ (nicotinamide adenine dinucleotide)](https://durgical.com/en/biochemistry/molecules/nad/)
- [Ubiquinone (coenzyme Q₁₀)](https://durgical.com/en/biochemistry/molecules/ubiquinone/)
- [Complex III (cytochrome bc₁)](https://durgical.com/en/biochemistry/enzymes/complex-iii/)
- [Succinate dehydrogenase (complex II)](https://durgical.com/en/biochemistry/enzymes/succinate-dehydrogenase/)
- [FAD (flavin adenine dinucleotide)](https://durgical.com/en/biochemistry/molecules/fad/)
- [Reactive oxygen species and antioxidants](https://durgical.com/en/biochemistry/topics/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [MT-ND1: NADH-ubiquinone oxidoreductase chain 1 (human)](https://www.uniprot.org/uniprotkb/P03886/entry) (UniProt, 2026); [Complex I biogenesis](https://reactome.org/PathwayBrowser/#/R-HSA-6799198) (Reactome, 2026); [MT-ND4 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/mt-nd4/) (MedlinePlus, US National Library of Medicine, 2026); [7VBZ: Matrix arm of active state CI from Rotenone-NADH dataset](https://www.rcsb.org/structure/7VBZ) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.

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