Autophagy

Autophagy (or autophagocytosis; from the Ancient Greek αὐτόφαγος, autóphagos, meaning "self-devouring"^[1] and κύτος, kýtos, meaning "hollow")^[2] is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism.^[3] It allows the orderly degradation and recycling of cellular components.^[4][5] Although initially characterized as a primordial degradation pathway induced to protect against starvation, it has become increasingly clear that autophagy also plays a major role in the homeostasis of non-starved cells.^[6] Defects in autophagy have been linked to various human diseases, including neurodegeneration and cancer, and interest in modulating autophagy as a potential treatment for these diseases has grown rapidly.^[6][7]

Four forms of autophagy have been identified: macroautophagy, microautophagy, chaperone-mediated autophagy (CMA), and crinophagy.^[8][9][10] In macroautophagy (the most thoroughly researched form of autophagy), cytoplasmic components (like mitochondria) are targeted and isolated from the rest of the cell within a double-membrane vesicle known as an autophagosome,^[11][12] which, in time, fuses with an available lysosome, bringing its specialty process of waste management and disposal; and eventually the contents of the vesicle (now called an autolysosome) are degraded and recycled. In crinophagy (the least well-known and researched form of autophagy), unnecessary secretory granules are degraded and recycled.^[8]

In disease, autophagy has been seen as an adaptive response to stress, promoting survival of the cell; but in other cases, it appears to promote cell death and morbidity. In the extreme case of starvation, the breakdown of cellular components promotes cellular survival by maintaining cellular energy levels.

The word "autophagy" was in existence and frequently used from the middle of the 19th century.^[13] In its present usage, the term autophagy was coined by Belgian biochemist Christian de Duve in 1963 based on his discovery of the functions of lysosome.^[3] The identification of autophagy-related genes in yeast in the 1990s allowed researchers to deduce the mechanisms of autophagy,^{[14][15][16][17][18]} which eventually led to the award of the 2016 Nobel Prize in Physiology or Medicine to Japanese researcher Yoshinori Ohsumi.^[19]