The complex I of the mitochondrial respiratory chain may also be referred as NADH:ubiquinone oxidoreductase or NADH dehydrogenase. It is the largest of the four respiratory chain complexes, having a higher size than a ribosome.
It is L-shaped, with 60 transmembrane domains and a hydrophilic peripheral region that contains the binding site of NADH and the redox centers. Complex I is composed by 44 distinct polypeptide chains, among them it is found a flavoprotein (with FMN as cofactor) and 8 iron-sulfur centers. Of these 44 proteins, 7 are encoded by mitochondrial DNA, while the remainder are encoded by nuclear DNA.
From the functional point of view, the complex I receives electrons from NADH and transfers them to ubiquinone. When I talk about NADH, I am referring to any mitochondrial NADH molecules, despite their origin, because NADH is associated reversibly to dehydrogenases. That means, after being formed inside the mitochondria, NADH can diffuse to reach the complex I, where it delivers the 2 electrons that it carries. During the transport of electrons along this complex, they are transferred to a protein which has as a FMN cofactor, originating FMNH2. Then, the electrons pass through various centers of iron-sulfur (Fe - S), until they reach the ubiquinone (Q ), which receives 2 electrons at a time, turning into ubiquinol (QH2).
During the transport of electrons along the complex I, there are small quantities of energy that are being released, which could not be used alone to produce ATP. Thus, our body retains some of that energy by creating a gradient of H+. That is, the energy that is released is used to actively transport H+ from the matrix to the intermembrane space. In the case of complex I, for every 2 electrons passing through it, 4 protons are pumped into the intermembrane space.
The chemical equation describing the action of complex I is:
NADH + 5H+(matrix) + Q → NAD+ + QH2 + 4H+ (intermembrane space)
There are several diseases caused by mutations in genes encoding components of complex I, namely, the Leber’s Hereditary Optic Neuropathy and Leigh syndrome.