Define the terms : Autophagy and Autolysis........
Autophagy is basically self eating. It refers to the breakdown of cellular components by the lysosomes and their digestion within the cell. This is of great value to the cell during period of starvation for survival.
Autolysis is self digestion. It is the breakdown of cells or tissues of an organism by the enzymes which are released within the organism itself. It causes cell death
Removal of cytoplasmic components, particularly membrane bounded organelles, by digesting them within secondary lysosomes (autophagic vacuoles). Particularly common in embryonic development and senescence.
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Autophagy, meaning ‘to eat oneself’, is one of the main mechanisms for maintaining cellular homeostasis. This pathway is not directly a death pathway, rather a self-cannibalisation pathway. Mediated via the lysosomal degradation pathway, autophagy is responsible for degrading cellular proteins and is currently the only known process for degrading cellular organelles, recycling them to ensure cell survival.
Research on autophagy has been on-going for over 40 years, but has been restricted by lack of knowledge about the molecular machinery behind this process. Over the last decade, huge advances have been made and genetic screens in yeast (s. cerevisiae) have led to the identification of over ~30 autophagy-related genes (ATG-genes), many of which have identified mammalian homologues (see table below) (1,2,3,4).
The term ‘Autophagy’ covers three processes; microautophagy, macroautophagy and chaperone-mediated autophagy (1):
- Microautophagy is the transfer of cytosolic components into the lysosome by direct invagination of the lysosomal membrane and subsequent budding of vesicles into the lysosomal lumen (17).
- Macroautophagy involves formation of a double-membrane structure called the autophagosome which sequesters cytosolic material and delivers it to the lysosome for degradation (18). Although this degradation can be selective (i.e. specific removal of damaged mitochondria sparing normal functioning ones) (19), degradation of soluble cytosolic proteins is non-selective.
- Chaperone-mediated autophagy (CMA) is characterised by its selectivity regarding the specific substrates (cytosolic proteins) degraded (20).
Autophagy is essential in helping to maintain the balance between the increase and decrease in the number of a cell population. It is undoubtedly active at a basal level in most cells and contributes to the routine turnover of cytoplasmic components (1, 21). Three predominant cellular functions can be assigned to autophagy:
- Autophagy is a response to nutrient starvation. Decreased levels of amino acids can induce the autophagic response in numerous cell types and situations e.g. the neonatal period, when the supply of nutrients via the milk has not yet replaced the nutrients via the placenta (6,7)
- Autophagy is a housekeeping process whereby long-lived proteins and organelles are recycled e.g. Mitochondria (22)
- Autophagy has tissue-specific roles e.g. during erythrocyte development, following nucleus expulsion, autophagy is required to degrade the remaining organelles. Degradation of the autophagic vesicle results in the functional biconcave shape (23, 24).
The Autophagic pathway