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autophagosome

Tuesday 14 February 2006

The autophagosome is the central organelle in macroautophagy, a vacuolar lysosomal catabolic pathway that degrades cytoplasmic material to fuel starving cells and eliminates intracellular pathogens.

Macroautophagy has important physiological roles during development, ageing and the immune response, and its cytoprotective function is compromised in various diseases.

A set of autophagy-related (ATG) proteins is hierarchically recruited to the phagophore, the initial membrane template in the construction of the autophagosome.

However, recent findings suggest that macroautophagy can also occur in the absence of some of these key autophagy proteins, through the unconventional biogenesis of canonical autophagosomes.

Autophagy

To survive extreme environmental conditions, and in response to certain developmental and pathological situations, eukaryotic organisms employ the catabolic process of autophagy.

This degradative pathway allows cells to eliminate large portions of the cytoplasm, from aberrant protein aggregates to superfluous or damaged organelles and even entire organisms such as invading bacteria.

Structures targeted for destruction are sequestered into large double-membrane vesicles called autophagosomes and then delivered into the interior of the lysosome or vacuole, where they are consumed by resident hydrolases.

Autophagosome formation during selective autophagy is dependent upon the cargoes, and in all cases seems to involve expansion of the sequestering membrane.

- Autophagy refers to lysosomal digestion of the cell’s own components. In this process, intracellular organelles and portions of cytosol are first sequestered from the cytoplasm in an autophagic vacuole formed from ribosome-free regions of the rough endoplasmic reticulum.

- The vacuole fuses with lysosomes or Golgi elements to form an autophagolysosome (autophagosome). Autophagy is a common phenomenon involved in the removal of damaged organelles during cell injury and the cellular remodeling of differentiation, and it is particularly pronounced in cells undergoing atrophy induced by nutrient deprivation or hormonal involution.

- The autophagic vacuoles are membrane-bound vacuoles within the cell that contain fragments of cell components (e.g., mitochondria, endoplasmic reticulum) that are destined for destruction and into which the lysosomes discharge their hydrolytic contents. The cellular components are then digested. Some of the cell debris within the autophagic vacuole may resist digestion and persist as membrane-bound residual bodies that may remain in the cytoplasm. An example of such residual bodies is the lipofuscin granules (lipofuscin deposits). When present in sufficient amounts, they impart a brown discoloration to the tissue (brown atrophy).

See also

- degradative patways

References

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