Atg8ylation As a General Membrane Stress and Remodeling Response

Overview

Journal Cell Stress

Date 2021 Sep 16

PMID 34527862

Citations 22

Authors

Suresh Kumar

Jingyue Jia

Vojo Deretic

Affiliations

Soon will be listed here.

Abstract

The yeast Atg8 protein and its paralogs in mammals, mammalian Atg8s (mAtg8s), have been primarily appreciated for their participation in autophagy. However, lipidated mAtg8s, including the most frequently used autophagosomal membrane marker LC3B, are found on cellular membranes other than autophagosomes. Here we put forward a hypothesis that the lipidation of mAtg8s, termed 'Atg8ylation', is a general membrane stress and remodeling response analogous to the role that ubiquitylation plays in tagging proteins. Ubiquitin and mAtg8s are related in sequence and structure, and the lipidation of mAtg8s occurs on its C-terminal glycine, akin to the C-terminal glycine of ubiquitin. Conceptually, we propose that mAtg8s and Atg8ylation are to membranes what ubiquitin and ubiquitylation are to proteins, and that, like ubiquitylation, Atg8ylation has a multitude of downstream effector outputs, one of which is autophagy.

Citing Articles

Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function.

Paddar M, Wang F, Trosdal E, Hendrix E, He Y, Salemi M Elife. 2025; 13.

PMID: 39773872 PMC: 11706607. DOI: 10.7554/eLife.100928.

Molecular Mechanisms Underlying Initiation and Activation of Autophagy.

Wei Z, Hu X, Wu Y, Zhou L, Zhao M, Lin Q Biomolecules. 2025; 14(12.

PMID: 39766224 PMC: 11673044. DOI: 10.3390/biom14121517.

Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function.

Paddar M, Wang F, Trosdal E, Hendrix E, He Y, Salemi M bioRxiv. 2024; .

PMID: 39026874 PMC: 11257513. DOI: 10.1101/2024.07.10.602886.

To eat or not to eat: a critical review on the role of autophagy in prostate carcinogenesis and prostate cancer therapeutics.

Kurganovs N, Engedal N Front Pharmacol. 2024; 15:1419806.

PMID: 38910881 PMC: 11190189. DOI: 10.3389/fphar.2024.1419806.

LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4 T lymphocytes.

Pradel B, Cantaloube G, Villares M, Deffieu M, Robert-Hebmann V, Lucansky V Autophagy. 2024; 20(8):1825-1836.

PMID: 38566318 PMC: 11262235. DOI: 10.1080/15548627.2024.2338573.

References

Young A, Chan E, Hu X, Kochl R, Crawshaw S, High S . Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci. 2006; 119(Pt 18):3888-900. DOI: 10.1242/jcs.03172. View

Maas S, Breakefield X, Weaver A . Extracellular Vesicles: Unique Intercellular Delivery Vehicles. Trends Cell Biol. 2016; 27(3):172-188. PMC: 5318253. DOI: 10.1016/j.tcb.2016.11.003. View

Ballabio A, Bonifacino J . Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat Rev Mol Cell Biol. 2019; 21(2):101-118. DOI: 10.1038/s41580-019-0185-4. View

Rapoport S, Hori M, KLATZO I . Reversible osmotic opening of the blood-brain barrier. Science. 1971; 173(4001):1026-8. DOI: 10.1126/science.173.4001.1026. View

Lee C, Lamech L, Johns E, Overholtzer M . Selective Lysosome Membrane Turnover Is Induced by Nutrient Starvation. Dev Cell. 2020; 55(3):289-297.e4. PMC: 8337093. DOI: 10.1016/j.devcel.2020.08.008. View

He C, Levine B . The Beclin 1 interactome. Curr Opin Cell Biol. 2010; 22(2):140-9. PMC: 2854269. DOI: 10.1016/j.ceb.2010.01.001. View

Tsukada M, Ohsumi Y . Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993; 333(1-2):169-74. DOI: 10.1016/0014-5793(93)80398-e. View

Bakula D, Muller A, Zuleger T, Takacs Z, Franz-Wachtel M, Thost A . WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy. Nat Commun. 2017; 8:15637. PMC: 5460038. DOI: 10.1038/ncomms15637. View

Ravenhill B, Boyle K, von Muhlinen N, Ellison C, Masson G, Otten E . The Cargo Receptor NDP52 Initiates Selective Autophagy by Recruiting the ULK Complex to Cytosol-Invading Bacteria. Mol Cell. 2019; 74(2):320-329.e6. PMC: 6477152. DOI: 10.1016/j.molcel.2019.01.041. View

10.

Florey O, Kim S, Sandoval C, Haynes C, Overholtzer M . Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes. Nat Cell Biol. 2011; 13(11):1335-43. PMC: 3223412. DOI: 10.1038/ncb2363. View

11.

Claude-Taupin A, Jia J, Mudd M, Deretic V . Autophagy's secret life: secretion instead of degradation. Essays Biochem. 2017; 61(6):637-647. DOI: 10.1042/EBC20170024. View

12.

Deretic V, Kroemer G . Autophagy in metabolism and quality control: opposing, complementary or interlinked functions?. Autophagy. 2021; 18(2):283-292. PMC: 8942406. DOI: 10.1080/15548627.2021.1933742. View

13.

Beale R, Wise H, Stuart A, Ravenhill B, Digard P, Randow F . A LC3-interacting motif in the influenza A virus M2 protein is required to subvert autophagy and maintain virion stability. Cell Host Microbe. 2014; 15(2):239-47. PMC: 3991421. DOI: 10.1016/j.chom.2014.01.006. View

14.

Nishimura T, Kaizuka T, Cadwell K, Sahani M, Saitoh T, Akira S . FIP200 regulates targeting of Atg16L1 to the isolation membrane. EMBO Rep. 2013; 14(3):284-91. PMC: 3589088. DOI: 10.1038/embor.2013.6. View

15.

Levine B, Kroemer G . Biological Functions of Autophagy Genes: A Disease Perspective. Cell. 2019; 176(1-2):11-42. PMC: 6347410. DOI: 10.1016/j.cell.2018.09.048. View

16.

Hornung V, Bauernfeind F, Halle A, Samstad E, Kono H, Rock K . Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008; 9(8):847-56. PMC: 2834784. DOI: 10.1038/ni.1631. View

17.

Otten E, Werner E, Crespillo-Casado A, Boyle K, Dharamdasani V, Pathe C . Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection. Nature. 2021; 594(7861):111-116. PMC: 7610904. DOI: 10.1038/s41586-021-03566-4. View

18.

Claude-Taupin A, Jia J, Bhujabal Z, Garfa-Traore M, Kumar S, da Silva G . ATG9A protects the plasma membrane from programmed and incidental permeabilization. Nat Cell Biol. 2021; 23(8):846-858. PMC: 8276549. DOI: 10.1038/s41556-021-00706-w. View

19.

Eapen V, Swarup S, Hoyer M, Paulo J, Harper J . Quantitative proteomics reveals the selectivity of ubiquitin-binding autophagy receptors in the turnover of damaged lysosomes by lysophagy. Elife. 2021; 10. PMC: 8523161. DOI: 10.7554/eLife.72328. View

20.

Broz P, Pelegrin P, Shao F . The gasdermins, a protein family executing cell death and inflammation. Nat Rev Immunol. 2019; 20(3):143-157. DOI: 10.1038/s41577-019-0228-2. View