Nutrient-regulated Phosphorylation of ATG13 Inhibits Starvation-induced Autophagy, Puente et al, 2016

Nutrient-regulated Phosphorylation of ATG13 Inhibits Starvation-induced Autophagy
Cindy Puente, Ronald C Hendrickson, Xuejun Jiang

Abstract
Autophagy is a conserved catabolic process that utilizes a defined series of membrane trafficking events to generate a de novo double-membrane vesicle termed the autophagosome, which matures by fusing to the lysosome. Subsequently, the lysosome facilitates the degradation and recycling of the cytoplasmic cargo.

In yeast, the upstream signals that regulate the induction of starvation-induced autophagy are clearly defined. The nutrient-sensing kinase Tor inhibits the activation of autophagy by regulating the formation of the Atg1-Atg13-Atg17 complex, through hyperphosphorylation of Atg13.

However, in mammals, the ortholog complex ULK1-ATG13-FIP200 is constitutively formed. As such, the molecular mechanism by which mTOR regulates mammalian autophagy is unknown.

Here we report the identification and characterization of novel nutrient-regulated phosphorylation sites on ATG13: Ser-224 and Ser-258. mTOR directly phosphorylates ATG13 on Ser-258 while Ser-224 is modulated by the AMPK pathway. In ATG13 knock-out cells reconstituted with an unphosphorylatable mutant of ATG13, ULK1 kinase activity is more potent, and amino acid starvation induced more rapid ATG13 and ULK1 translocation. These events culminated in a more rapid starvation-induced autophagy response.

Therefore, ATG13 phosphorylation plays a crucial role in autophagy regulation.

Link | PDF

 

https://pubmed.ncbi.nlm.nih.gov/27973551/

Rapamycin dephosphorylates ATG13 on paper but didn’t help me

 

AMPK is involved in lots of signalling roles. It can be triggered by low levels of ATP and is also involved in clock gene signalling . When I was a student I spent a morning in the library looking into it as it seemed to tick a lot of boxes

There is a fair bit on mTOR ( also FoX and SERT) genes and pathways on anti aging research and " science-y " nutraceuticals podcasts etc ( that are anti aging focussed) .

ETA - anti aging re autophagy and fasting