Mitochondrial electron transport and ATP synthesis

BIOL2210 Overview

  • Instructor: Prof Alison Baker

  • Topic: Mitochondrial electron transport and ATP synthesis

Learning Objectives

  • Understand processes in each protein complex of the mitochondrial electron transport chain (ETC).

  • Comprehend how these reactions establish a proton gradient.

  • Learn how ATP is synthesized via chemiosmosis.

Recommended Reading

  • Lodish et al., 8th Edition: Chapter 12 (Available online via library on and off campus via Kortext).

  • Voet, Voet, and Pratt, 4th Edition: Chapter 18 (Available via EBL or Laidlaw).

  • Biochemistry by Berg, Tymoczko, and Stryer, 9th Edition: Chapter 18 (Available online via library).

  • These texts reinforce lecture material.

Recap from 1st Year

  • Location: Mitochondrial inner membrane hosts the ETC.

  • Arrangement: Electron transfer components ordered by standard reduction potential from negative to positive.

  • Function: Redox reactions release energy to pump protons from matrix to intermembrane space, establishing a proton gradient that drives ATP synthesis.

Mitochondrial Electron Transport Chain

  • Visualizes the components and proton flow.

  • Major components:

    • Complex I (NADH-Q oxidoreductase)

    • Complex II (Succinate-Q oxidoreductase)

    • Complex III (Q-cytochrome c oxidoreductase)

    • Complex IV (Cytochrome c oxidase)

Redox Active Molecules in ETC

  • Key components include Flavins, Iron-sulfur (FeS) centers, Quinones, Cytochromes, and Copper centers.

  • Some carry hydrogen (H+ + e-), while others carry electrons only.

Oxidation States of Flavins

  • Flavin Mononucleotide (FMN):

    • Oxidized: FMN

    • Reduced: FMNH2 (carries hydrogen).

Types of Iron-Sulphur Clusters

  • Iron can exist in oxidation states Fe2+ and Fe3+, facilitating electron transfer.

  • Cysteine residues bind the FeS cluster in polypeptides.

Complex I: NADH-Q Oxidoreductase

  • Size: 1 MDa.

  • Composition: 14 central and ~30 peripheral subunits (mixture of mitochondrial and nuclear encoded).

  • Function: Ubiquinone reduction induces conformational changes, translocating 4 H+ per pair of electrons.

Complex II: Succinate Dehydrogenase

  • Functions in oxidizing succinate; no protons are pumped by complex II.

  • Reaction: Succinate + FAD+ → fumarate + FADH2.

Complex III: Q-Cytochrome C Oxidoreductase

  • Unique coordination stabilizes the reduced form and influences potential.

  • Overall Reaction: QH2 + 2 Cyt c ox + 2 H+ (matrix) → Q + 2 Cyt c red + 4 H+ (cytosol).

Complex IV: Cytochrome C Oxidase

  • Catalyzes the reduction of O2, critical for electron transfer.

  • Mechanism: Electron transfer facilitates binding of O2 and eventual release of H2O.

ATP Synthesis Recap

  • Coupling of electron transport and ATP synthesis via proton gradient.

  • Inhibition of either process stops the other.

  • Uncouplers allow electron flow without ATP synthesis by dissipating the gradient.

Structure of ATP Synthase

  • F1 Component: Composed of 3 alpha and 3 beta subunits; beta is catalytic.

  • Fo Component: Forms a H+ channel with hydrophobic proteins.

  • Proton flow drives rotation necessary for ATP synthesis.

Binding Change Mechanism of ATP Synthesis

  • Beta subunits change conformation as the gamma subunit rotates.

  • Produces 3 ATP per 360° rotation.

P:O Ratios

  • The P:O ratio indicates the number of ATP produced per oxygen reduced.

  • NADH-linked substrates yield a P:O ratio of approximately 2.7, while FADH2-linked substrates yield approximately 1.6.

  • Variability in industrial ATP synthases based on structural differences (e.g., c subunits).

Recap IV

  • Mechanisms of electron transfer and ATP synthesis are critical.

  • Protons drive rotation and conformational changes within ATP synthase for ATP production.