Sunday 9 January 2005
Mitochondrial dysfunction plays an important role in cell injury and apoptosis. In addition, various alterations in the number, size, and shape of mitochondria occur in some pathologic conditions. For example, in cell hypertrophy and atrophy, there is an increase and decrease, respectively, in the number of mitochondria in cells.
Mitochondria may assume extremely large and abnormal shapes (megamitochondria), as can be seen in the liver in alcoholic liver disease and in certain nutritional deficiencies.
Abnormalities of mitochondria are now recognized as the basis of many genetic diseases. In certain inherited metabolic diseases of skeletal muscle, the mitochondrial myopathies, defects in mitochondrial metabolism are associated with increased numbers of mitochondria that are often unusually large, have abnormal cristae, and contain crystalloids.
In addition, certain benign tumors found in salivary glands, thyroid, parathyroids, and kidneys consist of cells (sometimes called "oncocytes") with abundant enlarged mitochondria, giving the cell a distinctly eosinophilic appearance.
Mitochondria are important targets for virtually all types of injurious stimuli, including hypoxia and toxins. Cell injury is frequently accompanied by morphologic changes in mitochondria.
Mitochondria can be damaged by different ways:
increases of cytosolic Ca2+
oxidative stress by ROS (reactive oxygen species)
breakdown of phospholipids through the phospholipase A2 and sphingomyelin pathways
lipid breakdown products as free fatty acids and ceramide
Mitochondrial damage often results in the formation of a high-conductance channel, the so-called mitochondrial permeability transition, in the inner mitochondrial membrane.
Although reversible in its early stages, this nonselective pore becomes permanent if the inciting stimuli persist, precluding maintenance of mitochondrial proton motive force, or potential.
Because maintenance of membrane potential is critical for mitochondrial oxidative phosphorylation, it follows that irreversible mitochondrial permeability transition is a deathblow to the cell.
Mitochondrial damage can also be associated with leakage of cytochrome c into the cytosol. Because cytochrome c is an integral component of the electron transport chain and can trigger apoptotic death pathways in the cytosol, this pathologic event is also likely to be a key determinant of cell death.
giant mitochondria with concentric cristae
- Exemple: myocytes in Barth syndrome
densely packed mitochondria with pale matrix
- Exemple: Alpers syndrome
increased number and size of mitochondria
- Exemple: Alpers syndrome
- Exemple: tyrosinemia