- Autophagy involves sequestration of cellular organelles into cytoplasmic autophagic vacuoles. (autophagosomes) that fuse with lysosomes and digest the enclosed material.
- Autophagy is an adaptive response that is enhanced during nutrient deprivation, allowing the cell to cannibalize itself to survive.
- Autophagosome formation is regulated by more than a dozen proteins that act in a coordinated, and sequential manner.
- Dysregulation of autophagy occurs in many disease states including cancers, inflammatory bowel diseases, and new rodegenerative disorders. Autophagy plays a role in host defense against certain microbes.
Abnormal Intracellular Depositions and Calcifications
- Abnormal deposits of materials in cells and tissues are the result of excessive intake or defective transport or catabolism.
- Deposition of lipids :
- Fatty change: Accumulation of free triglycerides in cells, resulting from excessive intake or defective transport (often because of defects in synthesis of transport proteins); manifestation of reversible cell injury
- Cholesterol deposition: Result of defective catabolism and excessive intake; in macrophages and smooth muscle cells of vessel walls in atherosclerosis
- Deposition of proteins: Reabsorbed proteins in kidney tubules; immunoglobulins in plasma cells
- Deposition of glycogen: In macrophages of patients with defects in lysosomal enzymes that break down glycogen (glycogen storage diseases)
- Deposition of pigments: Typically indigestible pigments, such as carbon, lipofuscin (breakdown product of lipid peroxidation), or iron (usually due to overload, as in hemosiderosis)
- Pathologic calcifications :
- Dystrophic calcification: Deposition of calcium at sites of cell injury and necrosis
- Metastatic calcification: Deposition of calcium in normal tissues, caused by hypercalcemia (usually a consequence of parathyroid hormone excess)
- Cellular aging results from a combination of accumulating cellular damage (e.g., by free radicals), reduced capacity to divide (replicative senescence), reduced ability to repair damaged DNA, and defective protein homeostasis
- Accumulation of DNA damage: Defective DNA repair mechanisms; conversely, caloric restriction activates DNA repair and is known to prolong aging in model organisms
- Replicative senescence: Reduced capacity of cells to divide secondary to progressive shortening of chromosomal ends (telomeres)
- Defective protein homeostasis: Resulting from impaired chaperone and proteasome functions.
- Nutrient sensing system: Caloric restriction increases longevity. Mediators may be reduced lGF-1 signaling and increases in sirtuins.
©Robbins Basic Pathology, Ninth edition