Cellular Organelles: Mitochondria

Mitochondria

• Occupy up to 20% of the cytoplasmic volume of a eukaryotic cell
• Dynamic organelles, changing shape, fusing, dividing, and moving about the cell constantly
• Highly associated with the microtubular cytoskeleton, determining their orientation and distribution in different cell types

Morphology

• Short, bacterium-like bodies, 1-2μm in length
• Can be viewed in living cells with fluorescent dyes, such as Mito-Tracker Red or rhodamine 123

Functions of Mitochondria

• Providing the cell with ATP generated by oxidative phosphorylation
• Involving in many other metabolic functions, including:
  • Heme biosynthesis
  • Synthesis of iron/sulfur (Fe/S) clusters
  • Steroid synthesis
  • Metabolism of fatty acids
  • Regulation of the cellular redox state
  • Calcium homeostasis
  • Amino acid metabolism
  • Carbohydrate metabolism
  • Protein catabolism
• Central regulators of programmed cell death (Apoptosis)

Endosymbiotic Theory

• Mitochondria are thought to have arisen after engulfment of a bacterium by the progenitor of eukaryotic cells
• Mammalian cells typically contain hundreds or thousands of mitochondria
• Number of mitochondria per cell depends on the metabolic requirements of that cell

Mitochondrial Membranes

• Surrounded by two membranes: outer and inner
• Outer membrane:
  • Contains a major integral protein, porin (voltage-dependent anion channels)
  • Freely permeable to ions and small molecules
• Inner membrane:
  • Surrounds the internal mitochondrial matrix compartment
  • Highly folded to form invaginations known as cristae
  • Contains proteins involved in:
    • Respiratory chain
    • ATP production
    • Transport of small molecules and ions

Cristae

• About 20 nm-wide membrane discs or tubules that protrude deeply into the matrix
• Contain the machinery for electron transport and ATP synthesis
• Membrane area available for oxidative phosphorylation is greatly increased by the folding of the inner membrane

Mitochondrial Genetic System

• Mitochondria contain their own genetic system
• Human mitochondrial genome is a circular, double-stranded DNA, 16,569 base pairs in length
• Contains 37 genes that encode:
  • 2 ribosomal RNAs (12S and 16S rRNA)
  • 22 transfer RNAs (tRNAs)
  • 13 proteins involved in electron transport and oxidative phosphorylation
• Mitochondrial genome is maternally inherited and has a much higher mutation rate than the nuclear genome

Mitochondria Import Most of Their Proteins From the Cytosol

• Human mtDNA encodes only 13 proteins
• Mammalian mitochondria contain approximately 1500 unique proteins
• Most mitochondrial proteins are encoded by nuclear genes and imported from the cytosol
• Mitochondrial precursor proteins contain specific targeting signals that direct them to the organelle

Protein Translocators in the Mitochondrial Membranes

• TOM, TIM, SAM, and OXA complexes are multimeric membrane protein assemblies that catalyze protein translocation across mitochondrial membranes
• The protein components of the TIM22 and TIM23 complexes are structurally related, suggesting a common evolutionary origin

Protein Import by Mitochondria

• The N-terminal signal sequence of the mitochondrial precursor protein is recognized by receptors of the TOM complex
• The protein is then translocated through the TIM23 complex and the signal sequence is cleaved off by a signal peptidase in the matrix space to form the mature protein