Mitochondrial Electron Transport Chain and Oxidative Phosphorylation

Chapter 18

Oxidative phosphorylation

ETC + ATP synthesis; the process where high-energy electrons from NADH/FADH₂ are transferred to O₂ while generating ATP.

Respiratory chain (ETC)

Four large protein complexes in the inner mitochondrial membrane that transfer electrons and pump protons.

Purpose of ETC

To capture the energy released by electron transfer and use it to pump protons and make ATP.

Why the ETC is in a membrane

The membrane holds complexes in order, traps the proton gradient, and allows ATP synthase to use it.

Mitochondrial matrix

Location of the citric acid cycle, fatty acid oxidation, and where ETC accepts electrons from NADH/FADH₂.

Intermembrane space

Region where ETC pumps protons to create the proton gradient.

Endosymbiotic origin of mitochondria

Mitochondria evolved from engulfed aerobic bacteria and contain their own DNA.

Reduction potential (E'₀)

Measure of how strongly a molecule wants electrons; NADH has low/negative E, O₂ has high/positive E.

Reductant (reducing agent)

Electron donor.

Oxidant (oxidizing agent)

Electron acceptor.

Driving force of ETC

The large difference in reduction potential between NADH/FADH₂ and O₂.

Complex I (NADH-Q oxidoreductase)

Accepts electrons from NADH, pumps 4H⁺, and passes electrons to coenzyme Q.

Complex II (Succinate-Q reductase)

Accepts electrons from FADH₂, transfers to Q, and does NOT pump protons.

Complex III (Q-cytochrome c oxidoreductase)

Transfers electrons from QH₂ to cytochrome c and pumps protons via the Q cycle.

Complex IV (Cytochrome c oxidase)

Accepts electrons from cytochrome c and reduces O₂ to H₂O while pumping protons.

Coenzyme Q (ubiquinone)

Lipid-soluble electron carrier that moves within the membrane; accepts electrons from Complex I and II.

Cytochrome c

Small soluble heme protein that carries electrons from Complex III to Complex IV.

Iron-sulfur clusters

ETC cofactors cycling between Fe²⁺/Fe³⁺ that transfer electrons without binding protons.

Q cycle

Mechanism in Complex III that funnels 2-electron QH₂ into 1-electron cytochrome c while pumping 4H⁺.

Respirasome

Supercomplex formed by ETC complexes that increases efficiency and limits intermediate diffusion.

Reactive oxygen species (ROS)

Superoxide, peroxide, hydroxyl radicals formed by partial reduction of oxygen.

Superoxide dismutase (SOD)

Enzyme that converts superoxide radicals into peroxide and oxygen.

Catalase

Enzyme that converts hydrogen peroxide into water and oxygen.

Chemiosmotic hypothesis

Proposes that ATP synthesis is powered by the proton gradient produced by the ETC.

Proton-motive force

Combination of chemical gradient (pH) and electrical gradient that drives ATP synthesis.

ATP synthase (Complex V)

Two-part enzyme that synthesizes ATP using the proton gradient.

F₀ subunit

Membrane proton channel that rotates as protons pass through.

F₁ subunit

Catalytic headpiece containing 3 β subunits that produce ATP.

Three β-subunit conformations

L (binds ADP + Pi), T (synthesizes ATP), O (releases ATP).

Binding-change mechanism

Rotation of the γ subunit forces β subunits through L → T → O states.

ATP per full rotation of ATP synthase

One full rotation produces three ATP molecules.

Cristae function

Increases inner membrane surface area and concentrates proton gradient near ATP synthase for efficiency.

Glycerol 3-phosphate shuttle

Transfers cytosolic NADH electrons into the ETC by converting them to FADH₂.

Malate-aspartate shuttle

More efficient shuttle that moves cytosolic NADH electrons into the matrix as NADH.

ATP-ADP translocase (ANT)

Exchanges ADP into the matrix for ATP moving out; essential for ATP export.

Phosphate carrier

Imports Pi into the matrix in exchange for OH⁻; required for ATP synthesis.

ATP synthasome

Functional unit composed of ATP synthase, ANT, and the phosphate carrier.

ATP yield per glucose

Approximately 30 ATP produced per fully oxidized glucose molecule.

Respiratory control (acceptor control)

ETC activity depends on ADP levels; low ADP slows ETC and CAC.

IF1 (inhibitory factor 1)

Inhibits ATP synthase during low oxygen to prevent ATP hydrolysis.

Why FADH₂ yields less ATP

Complex II does not pump protons, so electron entry yields a smaller proton gradient.

Where most ATP comes from

Oxidative phosphorylation produces ~26 of the ~30 ATP generated per glucose.

Electron transfer and distance

Electron transfer slows as distance increases; proteins position cofactors to optimize rate.

Ultimate determinant of respiration rate

The cell's ATP demand.