The nonautophagic functions of autophagy-related proteins

ABSTRACTMacroautophagy/autophagy is an evolutionarily conserved degradation process in eukaryotic cells that destroys obsolete proteins and damaged organelles via lysosome action. Autophagy is regulated by multiple ATG (autophagy related) proteins, which are activated in distinct steps. Although the mechanisms by which ATGs regulate autophagy have been comprehensively studied, an increasing number of studies have demonstrated that, in addition to their canonical roles in regulating autophagy, ATGs still show several nonautophagic functions that are required for the maintenance of cellular homeostasis in eukaryotes. Therefore, intensive exploration into the nonautophagic roles of ATGs is essential for a complete understanding of the biological functions of ATGs. In addition, the results of these explorations may contribute to the development of therapeutic strategies for disorders related to the dysfunctions of ATGs. Here, in this review, we specifically focus on nonautophagic functions of ATGs and comprehensively summarize the research progresses related to ATGs, especially their regulatory effects on cell proliferation, differentiation, senescence and death; cargo transport and phagocytosis; immune responses; metabolic homeostasis; gene transcription; genome stability; and signal transduction. We believe that this review meaningfully contributes to understanding the roles and mechanisms by which ATGs regulate physiological and pathological processes.Abbreviations ATG: autophagy related; BECN1: beclin 1; cAMP: cyclic adenosine monophosphate; dsDNA: double-stranded DNA; EMT: epithelial-mesenchymal transition; IFN: interferon; ISCs: intestinal stem cells; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK/JNK: mitogen-activated protein kinase/c-Jun N-terminal kinases; MTOR: mechanistic target of rapamycin kinase; STING1: stimulator of interferon response cGAMP interactor 1; UVRAG: UV radiation resistance associated; VPS: vacuolar protein sorting.KEYWORDS: autophagy-related proteinsnonautophagic functionscargo transportcell growth and senescencemetabolic homeostasissignal transduction AcknowledgementsThe authors would like to thank all members of the Chen lab for discussions and supports.The authors apologize to colleagues whose work could not be cited due to space constraints.Disclosure statementNo potential conflict of interest was reported by the authors.Data availability statementNo data was used for the research described in the article.Additional informationFundingThis review was supported by the National Natural Science Foundation of China [Grant No.: 81972650 and 82273067], the Henan Provincial Natural Science Foundation [Grant No.: 222300420028 and 222300420120].