Downregulation of autophagy by Met30-mediated Atg9 ubiquitination
Year: 2020
Type: article
Abstract: Macroautophagy/autophagy is a highly conserved eukaryotic molecular process that facilitates the recycling of superfluous cytoplasmic materials, damaged organelles, and invading pathogens, resulting in proper cellular homeostasis and survival during stress conditions. Autophagy is stringently regulated at multiple stages, including control at transcriptional, translational, and posttranslational levels. In this work, we identified a mechanism by which regulation of autophagy is achieved through the posttranslational modification of Atg9. Here, we show that, in order to limit autophagy to a low, basal level during normal conditions, Atg9 is ubiquitinated and subsequently targeted for degradation in a proteasome-dependent manner through the action of the E3 ligase Met30. When cells require increased autophagy flux to respond to nutrient deprivation, the proteolysis of Atg9 is significantly reduced. Overall, this work reveals an additional layer of mechanistic regulation that allows cells to further maintain appropriate levels of autophagy and to rapidly induce this process in response to stress.
Institutions: University of Michigan, University of Fribourg
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G2457434316, G4060900387, Stimulus- and time-dependent protein dynamics in autophagy analyzed by quantitative mass spectrometry, G4648230081, G5099844066, Stimulus and time-dependent protein dynamics in autophagy analyzed by quantitative mass spectrometry, Characterization of Biomolecules by Mass Spectrometry, G8690818240, The mechanism and regulation of autophagy
OpenAlex ID: W3115150918