Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery
Since their initial discovery around two decades ago, the yeast autophagy-related (Atg)8 protein and its mammalian homologues of the light chain 3 (LC3) and γ-aminobutyric acid receptor associated proteins (GABARAP) families have been key for the tremendous expansion of our knowledge about...
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doaj-3b3690a6497a4faf9deb4a17f67f35852020-11-24T20:45:00ZengMDPI AGCells2073-44092019-08-018997310.3390/cells8090973cells8090973Mechanisms and Pathophysiological Roles of the ATG8 Conjugation MachineryAlf Håkon Lystad0Anne Simonsen1Department of Molecular Medicine, Institute of Basic Medical Sciences and Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 1112 Blindern, 0317 Oslo, NorwayDepartment of Molecular Medicine, Institute of Basic Medical Sciences and Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 1112 Blindern, 0317 Oslo, NorwaySince their initial discovery around two decades ago, the yeast autophagy-related (Atg)8 protein and its mammalian homologues of the light chain 3 (LC3) and γ-aminobutyric acid receptor associated proteins (GABARAP) families have been key for the tremendous expansion of our knowledge about autophagy, a process in which cytoplasmic material become targeted for lysosomal degradation. These proteins are ubiquitin-like proteins that become directly conjugated to a lipid in the autophagy membrane upon induction of autophagy, thus providing a marker of the pathway, allowing studies of autophagosome biogenesis and maturation. Moreover, the ATG8 proteins function to recruit components of the core autophagy machinery as well as cargo for selective degradation. Importantly, comprehensive structural and biochemical in vitro studies of the machinery required for ATG8 protein lipidation, as well as their genetic manipulation in various model organisms, have provided novel insight into the molecular mechanisms and pathophysiological roles of the mATG8 proteins. Recently, it has become evident that the ATG8 proteins and their conjugation machinery are also involved in intracellular pathways and processes not related to autophagy. This review focuses on the molecular functions of ATG8 proteins and their conjugation machinery in autophagy and other pathways, as well as their links to disease.https://www.mdpi.com/2073-4409/8/9/973ATG8LC3GABARAPATG5ATG7ATG16L1autophagyLAP |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alf Håkon Lystad Anne Simonsen |
spellingShingle |
Alf Håkon Lystad Anne Simonsen Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery Cells ATG8 LC3 GABARAP ATG5 ATG7 ATG16L1 autophagy LAP |
author_facet |
Alf Håkon Lystad Anne Simonsen |
author_sort |
Alf Håkon Lystad |
title |
Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery |
title_short |
Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery |
title_full |
Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery |
title_fullStr |
Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery |
title_full_unstemmed |
Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery |
title_sort |
mechanisms and pathophysiological roles of the atg8 conjugation machinery |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2019-08-01 |
description |
Since their initial discovery around two decades ago, the yeast autophagy-related (Atg)8 protein and its mammalian homologues of the light chain 3 (LC3) and γ-aminobutyric acid receptor associated proteins (GABARAP) families have been key for the tremendous expansion of our knowledge about autophagy, a process in which cytoplasmic material become targeted for lysosomal degradation. These proteins are ubiquitin-like proteins that become directly conjugated to a lipid in the autophagy membrane upon induction of autophagy, thus providing a marker of the pathway, allowing studies of autophagosome biogenesis and maturation. Moreover, the ATG8 proteins function to recruit components of the core autophagy machinery as well as cargo for selective degradation. Importantly, comprehensive structural and biochemical in vitro studies of the machinery required for ATG8 protein lipidation, as well as their genetic manipulation in various model organisms, have provided novel insight into the molecular mechanisms and pathophysiological roles of the mATG8 proteins. Recently, it has become evident that the ATG8 proteins and their conjugation machinery are also involved in intracellular pathways and processes not related to autophagy. This review focuses on the molecular functions of ATG8 proteins and their conjugation machinery in autophagy and other pathways, as well as their links to disease. |
topic |
ATG8 LC3 GABARAP ATG5 ATG7 ATG16L1 autophagy LAP |
url |
https://www.mdpi.com/2073-4409/8/9/973 |
work_keys_str_mv |
AT alfhakonlystad mechanismsandpathophysiologicalrolesoftheatg8conjugationmachinery AT annesimonsen mechanismsandpathophysiologicalrolesoftheatg8conjugationmachinery |
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1716815875769630720 |