Autophagocytosis

from Wikipedia, the free encyclopedia

Autophagocytosis or autophagy (from ancient Greek αὐτόφαγος autóphagos "self-consuming" and κύτος kýtos "cavity, space") describes the process in cells with which they break down and use their own components. This ranges from misfolded proteins to whole cell organelles. A related process is phagocytosis (a form of endocytosis ), in which substances are absorbed and used from outside the cell.

The Japanese scientist Yoshinori Ōsumi was awarded the Nobel Prize in Physiology or Medicine in 2016 for his discoveries in the field .

properties

Scheme of macroautophagy, EM uptake (bottom left) and fluorescence- labeled autophagosomes in liver cells
Schematic comparison of macro and microautophagy

Autophagocytosis occurs in many eukaryotes such as plants, multicellular animals , slime molds, and yeasts . The process is necessary for a balance between the production of new and the breakdown of old cell components. A mitochondrion of a liver cell, for example, has a lifespan of ten days before it is broken down by autophagy ( mitophagy , partly via omegasomes ) and its components are used again to build up other structures ( salvage pathway ). Thus, autophagy is a strategy developed by cells in the course of evolution to save energy.

Autophagocytosis is involved in the breakdown and remodeling of proteins and lipids and in the provision of amino acids when there is reduced or (partial) abstinence from food intake, as is the case with fasting . Fasting causes autophagy. It occurs to a small extent in all cells , but is increased in the case of metabolic , genotoxic , infectious and hypoxic stress.

As a cell gets older, autophagocytosis decreases. Autophagocytosis is involved, among other things, in the metastasis of tumors . Furthermore, a change in autophagy in the development of ALS , Alzheimer's disease , Huntington's disease , SENDA ( static encephalopathy of childhood with neurodegeneration in adulthood = Static encephalopathy childhood neurodegeneration in adulthood), multiple sclerosis , Crohn's disease and systemic lupus erythematosus (SLE) involved. Sorafenib leads to increased autophagy. Hydroxychloroquine and other chloroquine derivatives inhibit autophagy. Autophagy is regulated , among other things, by the protein autophagin 4A .

The processes of autophagy be roughly divided into three groups: the Makroautophagozytose or macroautophagy that Mikroautophagozytose or micro-autophagy and the chaperone -mediated autophagy ( chaperone mediated autophagy , CMA).

Macroautophagy

Macroautophagy is the main mechanism of autophagy and is used to break down cell organelles and proteins. Part of the membrane of the endoplasmic reticulum (ER) encloses the structures marked for degradation until the organelle to be degraded is completely enclosed by a double biomembrane . The resulting autophagosome is then along the actin - cytoskeleton transported until it is finally membrane fusion binds to a lysosome and its contents by lysosomal acid hydrolases is degraded.

Microautophagy

Microautophagy describes the direct uptake into the lysosome through the lysosomal membrane. The lysosomal membrane is turned inside out.

Chaperone-mediated autophagy

In the chaperone mediated autophagy ( chaperones mediated autophagy , CMA) proteins are a KFERQ-like motif of the chaperone or heat shock protein hsc70 recognized and performed as a protein complex to the lysosome where they through the lysosomal membrane-associated protein 2 (LAMP-2A) enter the lysosome and be broken down. The complex is absorbed into the lysosome through a receptor , with the Hsc70 serving as a chaperone for the unfolding of the imported proteins. Altered chaperone-mediated autophagy is involved in the development of Parkinson's disease .

Role in the immune system

Autophagocytosis also enables the intracellular breakdown of viruses , bacteria and foreign proteins that have entered the cell. With the breakdown, it also serves the immune response , because then the antigen is presented via MHC I and II. Various intracellular bacterial pathogens have developed resistance mechanisms to breakdown through autophagocytosis.

Participation in the life cycle change of some species

In insects, the process is used to transform the larval tissue into the adult form . Here, the tissue is melted down during pupation and rearranged to form the adult animal.

There are two signals that trigger this process: A lack of nutrients leads to the breakdown of non-essential cell components. This means that vital processes continue to be supplied with energy. An oversupply of nutrients can also trigger autophagocytosis. Then new organelles are formed with the excess energy and old ones are reused.

Autophagocytosis can also cause cells to die. It is part of programmed cell death ( apoptosis , autophagic cell death ). It thus regulates the growth of multicellular organisms and colonies (yeast).

Inhibition

Autophagy can be caused by certain drugs, such as chloroquine or hydroxychloroquine , inhibit . This opens up various therapeutic applications, for example in the chemotherapy of cancer diseases .

Reinforcement

The dietary agent spermidine has an intensifying effect on autophagocytosis.

history

Autophagocytosis was first described in 1962 by Keith R. Porter and his student Thomas Ashford . The breakdown and reuse of cellular components in the lysosome was described in 1963. The term autophagy was coined by Christian de Duve in 1963 at the Ciba Foundation Symposium on Lysosomes (February 12-14 ). In 1967 de Duve described glucagon- induced autophagocytosis in lysosomes of rat liver cells.

In the 1990s, various genes were described in yeast whose proteins are involved in autophagocytosis. The research groups of Yoshinori Ōsumi and Michael Thumm investigated hunger-induced nonselective autophagy. Daniel J. Klionsky discovered the cytoplasm-to-vacuole targeting signaling (CVT) pathway. It was the same mechanism. In 1999 the association of autophagy with cancer was described by Beth Levine's group . Originally, the genes involved in autophagy were given different names (APG, AUT, CVT, GSA, PAG, PAZ and PDD). In 2003 a unified nomenclature was adopted in which the autophagy genes are named ATG . The 2016 Nobel Prize in Medicine or Physiology was awarded to Yoshinori Ōsumi for his discoveries about autophagy. While the importance of Ōsumi's findings is widely recognized, the lack of involvement of other scientists involved in the award was criticized.

See also

literature

  • Vojo Deretic and Daniel J. Klionsky : Cleaning up the cell. In: Spectrum of Science, December 2008, p. 58.
  • Christiane Richter-Landsberg: Autophagy as a survival strategy in: Biology in our time, 6/2012, p. 374.
  • Irina Caminschi, Christian Münz: Autophagy for Better or Worse During Infectious Diseases. In: Frontiers in Immunology. 4, 2013, S., doi: 10.3389 / fimmu.2013.00205 .
  • JH Hurley, E. Nogales: Next-generation electron microscopy in autophagy research. In: Current opinion in structural biology. [Electronic publication before printing] September 2016, doi : 10.1016 / j.sbi.2016.08.006 , PMID 27614295 .
  • P. Lapaquette, J. Guzzo, L. Bretillon, MA Bringer: Cellular and Molecular Connections between Autophagy and Inflammation. In: Mediators of inflammation. Volume 2015, 2015, p. 398483, doi : 10.1155 / 2015/398483 , PMID 26221063 , PMC 4499609 (free full text).

Web links

Wiktionary: autophagocytosis  - explanations of meanings, word origins, synonyms, translations

Individual evidence

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