![]() ![]() This was the first time the fact that lysosomes are the sites of intracellular autophagy was established. With his student Russell Deter, he established that lysosomes are responsible for glucagon-induced autophagy. Unlike Porter and Ashford, de Duve conceived the term as a part of lysosomal function while describing the role of glucagon as a major inducer of cell degradation in the liver. Inspired by this discovery, de Duve christened the phenomena "autophagy". Hruban, Spargo and colleagues recognized three continuous stages of maturation of the sequestered cytoplasm to lysosomes, and that the process was not limited to injury states that functioned under physiological conditions for "reutilization of cellular materials", and the "disposal of organelles" during differentiation. In 1963 Hruban, Spargo and colleagues published a detailed ultrastructural description of "focal cytoplasmic degradation", which referenced a 1955 German study of injury-induced sequestration. Lysosomes could not be cell organelles, but part of cytoplasm such as mitochondria, and that hydrolytic enzymes were produced by microbodies. However Porter and Ashford wrongly interpreted their data as lysosome formation (ignoring the pre-existing organelles). They called this autolysis after Christian de Duve and Alex B. In January 1962 they reported an increased number of lysosomes in rat liver cells after the addition of glucagon, and that some displaced lysosomes towards the centre of the cell contained other cell organelles such as mitochondria. Porter and his student Thomas Ashford at the Rockefeller Institute. History Īutophagy was first observed by Keith R. The identification of autophagy-related genes in yeast in the 1990s allowed researchers to deduce the mechanisms of autophagy, which eventually led to the award of the 2016 Nobel Prize in Physiology or Medicine to Japanese researcher Yoshinori Ohsumi. 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. The word "autophagy" was in existence and frequently used from the middle of the 19th century. In the extreme case of starvation, the breakdown of cellular components promotes cellular survival by maintaining cellular energy levels. 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 crinophagy (the least well-known and researched form of autophagy), unnecessary secretory granules are degraded and recycled. 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, 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. įour forms of autophagy have been identified: macroautophagy, microautophagy, chaperone-mediated autophagy (CMA), and crinophagy. 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. 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. It allows the orderly degradation and recycling of cellular components. A Diagram of the process of autophagy, which produces the structures autophagosomes (AP), and autolysosomes (AL) B Electron micrograph of autophagic structures AP and AL in the fat body of a fruit fly larva C Fluorescently-labeled autophagosomes AP in liver cells of starved mice.Īutophagy (or autophagocytosis from the Ancient Greek αὐτόφαγος, autóphagos, meaning "self-devouring" and κύτος, kýtos, meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. ![]()
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