TY - JOUR
T1 - Canonical and non-canonical roles for ATG8 proteins in autophagy and beyond
AU - Reid, Steven Edward
AU - Kolapalli, Srinivasa Prasad
AU - Nielsen, Thorbjørn M.
AU - Frankel, Lisa B.
N1 - Funding Information:
This manuscript was funded by Lundbeckfonden (R272-2017-3872), Novo Nordisk Fonden (NNF19OC0057772) and Kræftens Bekæmpelse (R269-A15420). Each of these sources supported salaries of the authors.
Publisher Copyright:
Copyright © 2022 Reid, Kolapalli, Nielsen and Frankel.
PY - 2022
Y1 - 2022
N2 - During autophagy, the ATG8 family proteins have several well-characterized roles in facilitating early, mid, and late steps of autophagy, including autophagosome expansion, cargo recruitment and autophagosome-lysosome fusion. Their discovery has importantly allowed for precise experimental monitoring of the pathway, bringing about a huge expansion of research in the field over the last decades. In this review, we discuss both canonical and non-canonical roles of the autophagic lipidation machinery, with particular focus on the ATG8 proteins, their post-translational modifications and their increasingly uncovered alternative roles mediated through their anchoring at different membranes. These include endosomes, macropinosomes, phagosomes and the plasma membrane, to which ATG8 proteins can bind through canonical or alternative lipidation. Beyond new ATG8 binding partners and cargo types, we also explore several open questions related to alternative outcomes of autophagic machinery engagement beyond degradation. These include their roles in plasma membrane repair and secretion of selected substrates as well as the physiological implications hereof in health and disease.
AB - During autophagy, the ATG8 family proteins have several well-characterized roles in facilitating early, mid, and late steps of autophagy, including autophagosome expansion, cargo recruitment and autophagosome-lysosome fusion. Their discovery has importantly allowed for precise experimental monitoring of the pathway, bringing about a huge expansion of research in the field over the last decades. In this review, we discuss both canonical and non-canonical roles of the autophagic lipidation machinery, with particular focus on the ATG8 proteins, their post-translational modifications and their increasingly uncovered alternative roles mediated through their anchoring at different membranes. These include endosomes, macropinosomes, phagosomes and the plasma membrane, to which ATG8 proteins can bind through canonical or alternative lipidation. Beyond new ATG8 binding partners and cargo types, we also explore several open questions related to alternative outcomes of autophagic machinery engagement beyond degradation. These include their roles in plasma membrane repair and secretion of selected substrates as well as the physiological implications hereof in health and disease.
KW - Atg8
KW - autophagy
KW - lipidation
KW - post-translational modification (PTM)
KW - secretory autophagy
KW - single membrane
U2 - 10.3389/fmolb.2022.1074701
DO - 10.3389/fmolb.2022.1074701
M3 - Review
C2 - 36601581
AN - SCOPUS:85145422547
VL - 9
JO - Frontiers in Molecular Biosciences
JF - Frontiers in Molecular Biosciences
SN - 2296-889X
M1 - 1074701
ER -