The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. 'Protein modifications: beyond the usual suspects' review series.
As a lysosomal/vacuolar degradative pathway that is conserved in eukaryotic organisms, autophagy mediates the turnover of long-lived proteins and excess or aberrant organelles. The main characteristic of autophagy is the formation of a double-membrane vesicle, the autophagosome, which envelops part of the cytoplasm and delivers it to the lysosome/vacuole for breakdown and eventual recycling of the degradation products. Among the approximately 30 autophagy-related (Atg) genes identified so far, there are two ubiquitin-like proteins, Atg12 and Atg8. Analogous to ubiquitination, Atg12 is conjugated to Atg5 by Atg7--an E1-like protein--and Atg10--an E2-like protein. Similarly, Atg7 and Atg3 are the respective E1-like and E2-like proteins that mediate the conjugation of Atg8 to phosphatidylethanolamine. Both Atg12-Atg5 and Atg8 localize to the developing autophagosome. The Atg12-Atg5 conjugate facilitates the lipidation of Atg8 and directs its correct subcellular localization. Atg8-phosphatidylethanolamine is probably a scaffold protein that supports membrane expansion and the amount present correlates with the size of autophagosomes.
Geng
Jiefei
J
Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Michigan 48109-2216, USA.
Klionsky
Daniel J
DJ
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
D020033:Protein Isoforms; D025801:Ubiquitin