-Lecture Notes on Mitochondria

Learning Outcomes

By the end of the lecture, you should be able to:

  • Outline the structure of the mitochondria, including the phospholipid-protein ratios.

  • Classify the role of the main compartments (Outer/Inner Membranes, Matrix, and Intermembrane Space).

  • Establish the role of mitochondria in ATP production through metabolic pathways.

  • Identify the genetic makeup, inheritance patterns, and the Endosymbiotic Theory.

  • Understand the consequences of mitochondrial dysfunction and associated pathologies.

Introduction to Mitochondria and Endosymbiotic Theory

  • Mitochondria are double-membrane-bound organelles vital for cellular respiration, often referred to as the "energy factories of the cell."

  • Endosymbiotic Theory: Mitochondria originated from aerobic prokaryotes (alphaproteobacteria) that were engulfed by a precursor eukaryotic cell.

  • Dimensions: Typically 0.5 to 1.0 micrometers (\mu m) in diameter.

  • Quantity: A single cell can contain from one to several thousand mitochondria, depending on metabolic demands (e.g., muscle cells have high concentrations).

Structural Components of Mitochondria

  1. Outer Membrane

  • Structure: Smooth membrane with a protein:phospholipid ratio of 1:1.

  • Permeability: Contains porins that allow diffusion of molecules up to 10,000 Daltons.

  1. Inner Membrane

  • Structure: Highly folded to form cristae. Protein:phospholipid ratio of 80:20.

  • Biochemical Signature: Rich in cardiolipin, making the membrane impermeable to ions (H^+).

  • Function:

    • Houses the Electron Transport Chain (ETC) complexes (I, II, III, and IV).

    • Houses ATP Synthase (Complex V).

  1. Intermembrane Space

  • Space between the two membranes.

  • Proton Gradient: Reservoir for protons (H^+) pumped out of the matrix.

  1. Mitochondrial Matrix

  • Contents:

    • Enzymes for the Citric Acid Cycle and fatty acid \beta-oxidation.

    • Mitochondrial ribosomes (70S structure, similar to bacteria).

    • Multiple copies of mitochondrial DNA (mtDNA).

Role of Mitochondria in Energy Production

Synthesis of ATP

  1. Glycolysis:

    • Occurs in the cytosol.

    • Converts glucose into 2 pyruvate molecules.

    • Net yield: 2 ATP and 2 NADH.

  2. Citric Acid Cycle (Krebs Cycle):

    • Pyruvate enters the matrix and is converted to Acetyl-CoA.

    • Per glucose, generates: 6 NADH, 2 FADH_2, 2 GTP/ATP.

  3. Oxidative Phosphorylation:

    • Electron Transport Chain: NADH and FADH_2 donate electrons. Oxygen (O_2) is the final electron acceptor, forming water (H_2O).

    • Chemiosmosis: Energy from electron transfer pumps H^+ into the intermembrane space, creating an electrochemical gradient.

    • ATP Synthase: Protons flow back into the matrix, driving ATP synthesis: ADP + P_i \rightarrow ATP.

Energy Yield Summary

  • Complete Oxidation of Glucose:

    • Glycolysis: 2 ATP

    • Citric Acid Cycle: 2 GTP/ATP

    • Oxidative Phosphorylation: ~26-32 ATP

    • Total: ~30 to 36 ATP per glucose molecule

Additional Functions of Mitochondria

  • Apoptosis: Mitochondria release Cytochrome c into the cytosol, which activates caspases.

Mitochondrial Genetics and Division

Genetic Makeup (mtDNA)

  • Structure: Small, circular, double-stranded genome (\sim 16.6 kb in humans).

  • Coding: Encodes 37 genes: 13 for respiratory chain proteins, 22 for tRNAs, and 2 for rRNAs.

Inheritance and Dynamics

  • Maternal Inheritance: Mitochondria are inherited from the mother because sperm mitochondria are destroyed after fertilization.

  • Heteroplasmy vs. Homoplasmy:

    • Homoplasmy: All mtDNA copies are identical.

    • Heteroplasmy: A mixture of wild-type and mutant mtDNA. Disease symptoms appear when a "threshold" of mutant mtDNA is reached.

Mitochondrial Diseases

  • Caused by mutations in mtDNA or nuclear DNA coding for mitochondrial proteins.

  • Tissues with high metabolic rates are most affected:

    • Leber's Hereditary Optic Neuropathy (LHON): Leading to blindness.

    • MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes.

    • Myopathy: Primary muscle weakness and exercise intolerance.