Complex I
Complex I[edit | edit source]
Complex I, also known as NADH:ubiquinone oxidoreductase, is the first enzyme of the mitochondrial electron transport chain (ETC). It plays a crucial role in cellular respiration, which is the process by which cells generate ATP, the primary energy currency of the cell.
Structure[edit | edit source]
Complex I is a large, L-shaped enzyme composed of 45 different subunits in mammals, with a total molecular weight of approximately 980 kDa. It is embedded in the inner mitochondrial membrane, with one arm of the L extending into the mitochondrial matrix and the other arm lying within the membrane.
Subunits[edit | edit source]
The subunits of Complex I can be divided into two main groups:
- Core subunits: These are conserved across species and are essential for the enzyme's catalytic activity. They include the NADH dehydrogenase module and the ubiquinone-binding module.
- Accessory subunits: These subunits are not directly involved in the catalytic process but are important for the assembly and stability of the complex.
Function[edit | edit source]
Complex I catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q10), a lipid-soluble electron carrier. This process is coupled with the translocation of protons (H⁺) from the mitochondrial matrix to the intermembrane space, contributing to the proton gradient used by ATP synthase to produce ATP.
Reaction[edit | edit source]
The overall reaction catalyzed by Complex I is:
- NADH + H⁺ + Q + 4H⁺_matrix → NAD⁺ + QH₂ + 4H⁺_intermembrane
This reaction involves the oxidation of NADH, the reduction of ubiquinone to ubiquinol (QH₂), and the pumping of four protons across the inner mitochondrial membrane.
Mechanism[edit | edit source]
The mechanism of Complex I involves several steps:
- Electron transfer: Electrons from NADH are transferred to flavin mononucleotide (FMN), then through a series of iron-sulfur (Fe-S) clusters to ubiquinone.
- Proton translocation: The energy released from electron transfer is used to pump protons across the membrane, although the exact mechanism of coupling is still under investigation.
Clinical Significance[edit | edit source]
Mutations in Complex I subunits can lead to a variety of mitochondrial diseases, including Leigh syndrome and Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). These conditions often result in severe neurological and muscular symptoms due to impaired ATP production.
Research and Therapeutics[edit | edit source]
Research into Complex I is ongoing, with studies focusing on its structure, function, and role in disease. Potential therapeutic approaches include the use of coenzyme Q10 supplements and other compounds that can bypass or stabilize Complex I function.
See Also[edit | edit source]
References[edit | edit source]
- Hirst, J. (2013). "Mitochondrial Complex I." Annual Review of Biochemistry, 82, 551-575.
- Sazanov, L. A. (2015). "A giant molecular proton pump: structure and mechanism of respiratory complex I." Nature Reviews Molecular Cell Biology, 16(6), 375-388.
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Contributors: Prab R. Tumpati, MD