Mitochondrial Function

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Mitochondrial Structure - Powerhouse Blueprint

  • "Powerhouse": Primary site of ATP synthesis (oxidative phosphorylation).
  • Double Membrane:
    • Outer Membrane (OMM): Smooth, permeable (due to porins).
    • Inner Membrane (IMM): Folded into cristae (↑ surface area). Houses ETC complexes & ATP synthase.

      ⭐ Cardiolipin in IMM makes it highly impermeable to ions, essential for maintaining the proton gradient.

  • Intermembrane Space (IMS): Located between OMM & IMM. Contains cytochrome c (apoptosis).
  • Matrix: Innermost space. Contains mtDNA, ribosomes, enzymes for TCA cycle, fatty acid oxidation.

Mitochondrion diagram with labeled parts

Electron Transport Chain - Electron Hustle

  • Location: Inner mitochondrial membrane (IMM).
  • Goal: Oxidize NADH & FADH₂; transfer electrons to $O_2$; pump $H^+$ from matrix to intermembrane space (IMS), creating proton-motive force.
  • Components:
    • Complex I (NADH dehydrogenase): NADH → CoQ. Pumps 4$H^+$.
    • Complex II (Succinate dehydrogenase): FADH₂ → CoQ. No $H^+$ pumping.
    • Coenzyme Q (Ubiquinone): Mobile electron carrier.
    • Complex III (Cytochrome bc₁ complex): CoQ → Cytochrome c. Pumps 4$H^+$.
    • Cytochrome c: Mobile electron carrier.
    • Complex IV (Cytochrome c oxidase): Cytochrome c → $O_2$. Pumps 2$H^+$. $O_2$ reduced to $H_2O$.
  • Electron Flow:
  • 📌 ETC Inhibitors: RotenONE (Complex I), AnAAmycin (Complex III), CO/CN⁻/H₂S IDE (Complex IV).

Electron Transport Chain and ATP Synthase

⭐ Cyanide (CN⁻) and Carbon Monoxide (CO) are potent inhibitors of Complex IV (Cytochrome c oxidase), halting electron transport and ATP synthesis, leading to rapid cellular hypoxia.

Oxidative Phosphorylation - Energy Mint

  • Mechanism: ATP synthesis fueled by energy from electron transfer (NADH/FADH₂ → O₂) via ETC on Inner Mitochondrial Membrane (IMM).
  • Chemiosmosis (Mitchell): ETC pumps H⁺ (matrix → Intermembrane Space/IMS), creating Proton-Motive Force (PMF; an electrochemical gradient).
  • ATP Synthase (Complex V; F₀F₁ ATPase):
    • F₀ (IMM): Proton channel for H⁺ re-entry to matrix.
    • F₁ (matrix): Catalytic sites; $ADP + P_i + H^+{matrix} \rightarrow ATP + H_2O + H^+{IMS}$.
  • P/O Ratios:
    • NADH: ~2.5 ATP (enters Complex I).
    • FADH₂: ~1.5 ATP (enters Complex II). ATP synthase structure, proton flow, and ATP synthesis
  • ⭐ > Uncouplers (e.g., 2,4-DNP, aspirin overdose) dissipate proton gradient, ↑O₂ consumption, ↓ATP synthesis, produce heat. (Thermogenin is a natural uncoupler).

Mito Dysfunction & Roles - When Power Fails

  • Dysfunction: Causes & Features
    • Genetic: mtDNA mutations (e.g., MELAS, LHON, MERRF); nuclear DNA gene defects.
    • Acquired: Ischemia/reperfusion, toxins (CN⁻, CO), drugs (zidovudine), ↑ROS.
    • Results in impaired oxidative phosphorylation (OXPHOS).
  • Consequences of Failure
    • ↓ATP synthesis: Energy crisis, particularly in high-demand tissues (brain, heart, muscle).
    • ↑ROS production: Oxidative stress, lipid peroxidation, further mtDNA damage.
    • Apoptosis initiation: Release of cytochrome c, activating caspases.
  • Beyond Energy: Critical Roles
    • $Ca^{2+}$ homeostasis: Sequesters and releases $Ca^{2+}$, shaping signals.
    • Metabolic pathways: Heme synthesis, steroid hormone synthesis (initial steps).
    • Thermoregulation: Non-shivering thermogenesis via UCP1 in brown adipose tissue.

⭐ Mitochondrial DNA (mtDNA) is exclusively maternally inherited and has a high mutation rate. Mitochondrial DNA (mtDNA) circular structure diagramoka

High‑Yield Points - ⚡ Biggest Takeaways

  • Mitochondria: Powerhouses; main site of ATP synthesis via oxidative phosphorylation.
  • Electron Transport Chain (ETC): Located on inner mitochondrial membrane (IMM).
  • Chemiosmosis: Proton gradient across IMM drives ATP synthase (Complex V).
  • Uncoupling proteins (e.g., thermogenin/UCP1) dissipate proton gradient, generating heat.
  • Mitochondrial DNA (mtDNA): Maternally inherited, circular; codes for some ETC components.
  • ETC Inhibitors: Rotenone (C-I), Antimycin A (C-III), CN-/CO (C-IV), Oligomycin (ATP synthase).
  • Role in apoptosis (cytochrome c release) and Ca2+ homeostasis.

Practice Questions: Mitochondrial Function

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An affected male does not have affected children but an affected female always has affected children. Type of inheritance?

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Flashcards: Mitochondrial Function

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What kind of transport systems follow stereospecificity?_____

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What kind of transport systems follow stereospecificity?_____

Carrier-mediated

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