Who first identified the process of autophagy?
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Christian de Duve coined the term autophagy in 1963 whereas Ohsumi began his work in 1988. Prior to that time, less than 20 papers per year were published on this subject. During the 1990s, Ohsumi's group described the morphology of autophagy in yeast, and performed mutational screening on yeast cells that identified essential genes for cells to be capable of autophagy.
Yoshinori Ohsumi
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Autophagy was first observed by Keith R. Porter and his student Thomas Ashford at the Rockefeller Institute. 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. They called this autolysis after Christian de Duve and Alex B. Novikoff. However Porter and Ashford wrongly interpreted their data as lysosome formation (ignoring the pre-existing organelles). Lysosomes could not be cell organelles, but part of cytoplasm such as mitochondria, and that hydrolytic enzymes were produced by microbodies. 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. 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. Inspired by this discovery, de Duve christened the phenomena "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. With his student Russell Deter, he established that lysosomes are responsible for glucagon-induced autophagy. This was the first time the fact that lysosomes are the sites of intracellular autophagy are established.
Autophagy
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The name "autophagy" was coined by Belgian biochemist Christian de Duve in 1963 based on his discovery of the functions of lysosome. The identification of autophagy-related genes in yeast in the 1990s let researchers figure out the mechanisms of autophagy, which eventually led to the award of the 2016 Nobel Prize in Physiology or Medicine to Japanese researcher Yoshinori Ohsumi.
Autophagy
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Autophagy (Greek: ‘self-eating’) was initially identified as a catabolic process for the unselective degradation of cellular content in lysosomes under starvation conditions. However, autophagy also comprises selective degradation pathways, which depend on ubiquitin conjugation to initiate sorting to lysosomes. In the case of chaperone-assisted selective autophagy, dysfunctional, nonnative proteins are recognized by molecular chaperones and become ubiquitinated by chaperone-associated ubiquitin ligases. The ubiquitinated proteins are enclosed in autophagosomes, which eventually fuse with lysosomes, leading to the degradation of the dysfunctional proteins. Chaperone-assisted selective autophagy is a vital part of the cellular protein quality control system. It is essential for protein homeostasis (proteostasis) in neurons and in mechanically strained cells and tissues such as skeletal muscle, heart and lung.
Chaperone-assisted selective autophagy
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The first autophagy genes were identified by genetic screens conducted in "Saccharomyces cerevisiae". Following their identification those genes were functionally characterized and their orthologs in a variety of different organisms were identified and studied.
Autophagy
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In October 2001, Cuervo accepted a faculty position at the Albert Einstein College of Medicine in The Bronx, New York. She then began primarily focusing on chaperone-mediated autophagy and its role in aging and human disease. Her research lab focused on protein translocations across lysosomal membranes, identifying regulator proteins like glial fibrillary acidic protein. In collaboration with neuroscientist David Sulzer of Columbia University Medical Center, she published evidence of altered chaperone-mediated autophagy in Parkinson's Disease. Similar findings of disrupted autophagy was also reported when Huntington Disease was studied. Cuervo's research team also identified LRRK2, a protein enzyme that becomes mutated in Parkinson's disease, disrupts the process of translocation across lysosomal membranes.
Ana Maria Cuervo
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Autophagy is the process by which the cells in an organism destroy non-functional or unnecessary self-components. Specifically, autophagy is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. Autophagy is also crucial for instances of starvation and removal of potentially dangerous cellular materials, indicating its necessity in maintaining life. As seen in the associated figure "Autophagy", cellular products are degraded by destructive cellular components, such as lysosomes, to produce new materials for the cell to use. Research into autophagy and its related processes has exploded over recent years, however, many of these processes processes are not completely understood and homologs have not been found in different species for many of these proteins. Its molecular mechanisms have not been fully elucidated, despite dramatic advances in the field as evidenced by hundreds of autophagy-related genes and proteins reported. As such, there was a demonstrated need for a database to characterize human autophagy proteins and components and/or their homologs, as well as orthologs in other species.
Autophagy database
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Rubinsztein has made major contributions to the field of neurodegeneration with his laboratory's discovery that autophagy regulates the levels of intracytoplasmic aggregate-prone proteins that cause many neurodegenerative diseases, including Huntington's, Parkinson's and Alzheimer's disease. His lab has found that autophagy may be inhibited in various neurodegenerative diseases and has elucidated the pathological consequences of autophagy compromise. In addition his research has advanced the basic understanding of autophagy, identifying the plasma membrane as a source of autophagosome membrane and characterising early events in autophagosome biogenesis. Furthermore, he studied how lysosomal positioning regulates autophagy. His goal is to understand the links between these diseases and autophagy. He is currently focused on understanding how to induce autophagy in vivo to remove toxic proteins and avoid the development of neurodegenerative disease
David C. Rubinsztein
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The field of autophagy research experienced accelerated growth at the turn of the 21st century. Knowledge of ATG genes provided scientists more convenient tools to dissect functions of autophagy in human health and disease. In 1999, a landmark discovery connecting autophagy with cancer was published by Beth Levine's group. To this date, relationship between cancer and autophagy continues to be a main theme of autophagy research. The roles of autophagy in neurodegeneration and immune defense also received considerable attention. In 2003, the first Gordon Research Conference on autophagy was held at Waterville. In 2005, Daniel J Klionsky launched "Autophagy", a scientific journal dedicated to this field. The first Keystone Symposia Conference on autophagy was held in 2007 at Monterey. In 2008, Carol A Mercer created a BHMT fusion protein (GST-BHMT), which showed starvation-induced site-specific fragmentation in cell lines. The degradation of betaine homo-cysteine methyltransferase (BHMT), a metabolic enzyme, could be used to assess autophagy flux in mammalian cells.
Autophagy
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Mitophagy is the selective degradation of mitochondria by autophagy. It often occurs to defective mitochondria following damage or stress. The process of mitophagy was first described over a hundred years ago by Lewis and Lewis. Ashford and Porter used electron microscopy to observe mitochondrial fragments in liver lysosomes by 1962, and a 1977 report suggested that "mitochondria develop functional alterations which would activate autophagy." The term "mitophagy" was in use by 1998.
Mitophagy
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Autophagy database is a product of the National Institute of Genetics (NIG) NIG was founded in June 1949 by the ministry of Education, Science, Sports, and Culture, with Prof. Kan Oguma being elected the first director. Over time, many departments have been added for various applications such as Genetics, Genomics, DNA Research, and, most notably for our purposes, the DNA Data Bank. NIG is a division of the Japanese Research Organization of Information and Systems, and is currently under the supervision of its ninth director. NIG aims to conduct top-level research in the pursuit of streamlining of information, as well as the dissemination of information from research into societal application. A tool created by this organization for this purpose is the Autophagy database.
The Autophagy database is a database of proteins involved in autophagy. The Autophagy database intends to collect all relevant information, organize it, and make it publicly available so that its users can easily get up-to-date knowledge. Specifically, the Autophagy database offers a "free-for-all" tool for those with interests, research and otherwise, in autophagy. To better accomplish this aim, the available Autophagy database from NIG calls for users of the database to disseminate and share information, so that autophagy-related data can be available for free to all who need it. For an interested research community, this model of research dissemination holds promise. As of , there were 582 reviewed proteins available in this database. Including autophagic proteins available in HomoloGene, NCBI, there are over 52,000 total proteins. Autophagy database offers comparison of homologous proteins between 41 different species to search new and old autophagy-related proteins, so that current autophagy research can be streamlined. The database was made publicly available in March 2010 and currently includes 7,444 genes/proteins in 82 eukaryotes.
Autophagy database