Mitochondrion Study Guide

📖 Core Concepts Mitochondrion – double‑membrane organelle that generates most cellular ATP via aerobic respiration. Inner membrane – site of the electron‑transport chain (ETC), ATP synthase, and highly impermeable (requires specific transporters). Cristae – folds of the inner membrane that dramatically increase surface area for oxidative phosphorylation. Matrix – lumen of the inner membrane; contains citric‑acid‑cycle enzymes, mtDNA, and mitochondrial ribosomes. Mitochondrial DNA (mtDNA) – circular 16 kb genome encoding 13 ETC proteins, 22 tRNAs, 2 rRNAs; maternally inherited. Mitochondria‑Associated ER Membrane (MAM) – contact site that mediates Ca²⁺ exchange, lipid trafficking, and signaling. Chemiosmosis – proton gradient generated by ETC complexes drives ATP synthesis via ATP synthase. Uncoupling – proton leak (e.g., via UCP1) dissipates the gradient as heat instead of ATP. Fission & Fusion – dynamic processes that remodel mitochondrial network, essential for quality control and distribution. --- 📌 Must Remember ATP yield: Aerobic respiration ≈ 13× more ATP per glucose than anaerobic fermentation. Citric‑acid‑cycle products per acetyl‑CoA: 3 NADH, 1 FADH₂, 1 GTP. ETC electron donors: NADH → Complex I; FADH₂ → Complex II. O₂ role: Final electron acceptor at Complex IV; reduced to H₂O. Proton pumping: Complex I, III, IV each pump protons → electrochemical gradient (Δp). mtDNA inheritance: Strictly maternal (sperm mitochondria ubiquitinated & degraded). Key mtDNA genes: 13 respiratory‑complex subunits, 22 tRNAs, 2 rRNAs. Apoptosis trigger: Release of cytochrome c from intermembrane space → caspase cascade. Calcium uniporter: Drives Ca²⁺ into matrix using membrane potential; stimulates dehydrogenases. MAM functions: Calcium signaling hub; phospholipid exchange; lipid trafficking. --- 🔄 Key Processes Aerobic respiration (overall) Glycolysis → pyruvate + NADH (cytosol) Pyruvate → acetyl‑CoA (matrix) Citric‑acid cycle → NADH, FADH₂, GTP (matrix) ETC → proton pumping → Δp ATP synthase uses Δp → ATP + H₂O Electron Transport Chain (ETC) Complex I (NADH dehydrogenase): NADH + H⁺ → ↑ e⁻; pumps 4 H⁺. Complex II (succinate dehydrogenase): FADH₂ → ↑ e⁻; no proton pumping. Complex III (cytochrome c reductase): transfers e⁻ to cytochrome c; pumps 4 H⁺. Complex IV (cytochrome c oxidase): e⁻ + ½ O₂ + 2 H⁺ → H₂O; pumps 2 H⁺. Chemiosmosis $$\text{ATP synthase: } ADP + Pi + 4H^+{\text{out}} \rightarrow ATP + H2O + 4H^+{\text{in}}$$ Mitochondrial calcium uptake Ca²⁺ enters matrix via the calcium uniporter (driven by ΔΨ). Elevated matrix Ca²⁺ activates isocitrate dehydrogenase, α‑KGDH, and PDH → ↑ NADH. Apoptosis (intrinsic pathway) Outer membrane permeabilization → cytochrome c release → apoptosome formation → caspase‑9 → executioner caspases. Fission & Fusion cycle Fission: DRP1 recruited to outer membrane → constriction → division. Fusion: MFN1/2 mediate outer‑membrane fusion; OPA1 mediates inner‑membrane fusion. --- 🔍 Key Comparisons Outer vs. Inner Membrane Outer: Contains VDAC, porous to ions/small molecules, protein import via TOM complex. Inner: Impermeable, houses ETC, ATP synthase, cardiolipin‑rich, no porins. Complex I vs. Complex II Complex I: Accepts electrons from NADH, pumps protons. Complex II: Accepts electrons from FADH₂, does not pump protons. Mitochondrial DNA vs. Nuclear DNA mtDNA: Circular, 16 kb, 37 genes, no introns, maternal inheritance. Nuclear DNA: Linear chromosomes, >20 k genes, biparental inheritance, encodes >99 % of mitochondrial proteins. Apoptosis vs. Necrosis Apoptosis: Controlled, cytochrome c release, caspase activation, DNA fragmentation. Necrosis: Uncontrolled membrane rupture, inflammation, no caspase cascade. --- ⚠️ Common Misunderstandings “Mitochondria make all the cell’s ATP.” – Only 90 % of ATP in aerobic cells; glycolysis also contributes, especially in hypoxic conditions. “All mitochondria have the same number of copies of mtDNA.” – Copy number varies widely (e.g., liver cells vs. sperm). “Uncoupling always wastes energy.” – In brown adipose tissue, intentional uncoupling (UCP1) generates heat for thermogenesis. “Mitochondrial diseases are always caused by mtDNA mutations.” – Many arise from nuclear‑encoded mitochondrial protein defects (e.g., Friedreich’s ataxia). --- 🧠 Mental Models / Intuition “Power plant” analogy: Outer membrane = loading dock; inner membrane = turbine hall (ETC pumps); cristae = stacked turbines increasing capacity. “Water dam” model for chemiosmosis: Proton gradient = water behind dam; ATP synthase = turbine that turns when water flows through. “Traffic flow” for calcium: MAM = highway interchange; ER releases Ca²⁺ (exit ramp) → uniporter (on‑ramp) → matrix (city). --- 🚩 Exceptions & Edge Cases Paternal mtDNA transmission – Rare in some bivalves, occasional human cases. Alternative mitochondrial genetic code – AUA, AUU, AUC can serve as start codons; some codon reassignments are due to RNA editing. Succinate dehydrogenase (Complex II) – Only ETC complex embedded in inner membrane but its enzyme activity also belongs to the citric‑acid cycle. --- 📍 When to Use Which Identify ATP source – If question mentions oxygen or “aerobic,” apply oxidative phosphorylation; if anaerobic, use glycolysis/fermentation. Choose membrane for transport – Small ions → diffuse through VDAC (outer); larger metabolites → specific inner‑membrane carriers. Select apoptosis trigger – Cytosolic cytochrome c release → intrinsic pathway; external Fas ligand → extrinsic pathway. Apply mtDNA vs. nuclear mutation reasoning – Phenotype affecting ETC subunits → suspect mtDNA; defects in assembly factors, import machinery → suspect nuclear gene. --- 👀 Patterns to Recognize High‑energy demand tissues → abundant mitochondria (e.g., liver, muscle, heart). Elevated uncoupling protein expression → brown adipose tissue or fever‑inducing conditions. mtDNA bottleneck → large variance in heteroplasmy among offspring. MAM‑related symptoms – calcium‑handling disorders, lipid‑metabolism defects. --- 🗂️ Exam Traps “Complex II pumps protons.” – It transfers electrons but does not pump protons; choose the answer that reflects this. “All mitochondria contain their own ribosomes.” – True, but remember most proteins are nuclear‑encoded and imported. “Mitochondrial DNA recombines like nuclear DNA.” – mtDNA undergoes virtually no recombination; answers suggesting frequent recombination are wrong. “Cytochrome c is a membrane protein.” – It is a soluble intermembrane‑space protein; only its release triggers apoptosis. “More cristae always mean more ATP per mitochondrion.” – Generally true, but ATP output also depends on substrate availability and membrane potential; cristae density alone is insufficient. ---