oxidative phosphorylation

Most of ATP production in mitochondria comes from oxidative phosphorylation. 

Electron transfer and ADP phosphorylation are not directly coupled to each other in the same electron complex, but by a proton motive force generated across the inner mitochondrial membrane (Mitchell, 1966). The proton-motive force is created by coupling movement of electrons through the electron transport chain (ETC) to proton pumping into the cytosol. Because the IMM is normally impermeable to protons, ATP synthase serves as the only route for protons to re-enter the matrix. Small membrane-soluble such as FCCP and dinitrophenol can uncouple respiration from ATP synthesis. 

Complex I is the largest enzyme complex, with 14-45 subunits depending on the source. All Complex I molecules imaged so far have an L-shaped structure, with a hydrophobic arm embedded in the IMM and one hydrophilic arm projecting into the matrix. Seven of the units in complex I are encoded by mtDNA. The primary electron acceptor of complex I is a flavin mononucleotide. It can be inhibited by rotenone. At Complex I, 4 protons are moves from cytosol to matrix, and ubiquinone is reduced to ubiquinol.

Complex II reduces succinate to fumarate as an enzymatic component of the TCA cycle. This causes its prosthetic group FAD to be reduced, then reoxidised by ubiquinol. No protons are pumped at Complex II, and it is the only component in the electron transport chain that is entirely nuclear-coded. Complex II contains 4 subunits in the mammal which carry a haem B. Reduction occurs at FAD which is then reoxidised by ubiquinone. It can be inhibited by antimycin A.

Complex III accepts electrons from ubiquinol at the UQH2 oxidation site. Electrons are transferred to cytochrome c. Mammalian complex III is a homodimer containing four redox-active prosthetic groups containing haem c and 2 haem Bs. The core of complex III is mtDNA-encoded cytochrome b.

Complex IV is a homodimer with a functional core containing 3 mtDNA-encoded core. The entry point for electrons is a bimetallic copper centre in subunit II; subunit I houses two haem a. One haem a3 forms the oxygen reduction site along with a histidine-ligated copper. Complex IV transfers electrons from reduced cytochrome c to molecular oxygen. Reduction to 2 water molecules requires movement of 4 electrons along with 4 protons, and each catalytic cycle moves 4 protons into the intermembrane space as well. Cyanide acts on complex IV to block all respiration regardless of concentration of substrate.

Complex V is (F1F0) ATP synthase. Proton translocation through Complex V is coupled to ATP synthesis. It can be inhibited by oligomycin.

#cell-biology

mitochondria