4.8 Article

Kog1/Raptor mediates metabolic rewiring during nutrient limitation by controlling SNF1/AMPK activity

Journal

SCIENCE ADVANCES
Volume 7, Issue 16, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abe5544

Keywords

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Funding

  1. SERB-NPDF postdoctoral fellowship from the Department of Science and Technology, Government of India [PDF/2016/001877]
  2. DBT-Wellcome Trust India Alliance fellowship [IA/I/14/2/501523]
  3. inStem/DBT

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In changing environments, cells modulate resource budgeting through distinct metabolic routes to control growth. The TORC1 and SNF1/AMPK pathways operate contrastingly in nutrient replete or limited environments to maintain homeostasis. Kog1, a modified form of yeast TORC1 component, plays a crucial role in regulating SNF1/AMPK activity and outputs during glucose and amino acid limitations, facilitating effective carbon allocation and metabolic flux.
In changing environments, cells modulate resource budgeting through distinct metabolic routes to control growth. Accordingly, the TORC1 and SNF1/AMPK pathways operate contrastingly in nutrient replete or limited environments to maintain homeostasis. The functions of TORC1 under glucose and amino acid limitation are relatively unknown. We identified a modified form of the yeast TORC1 component Kog1/Raptor, which exhibits delayed growth exclusively during glucose and amino acid limitations. Using this, we found a necessary function for Kog1 in these conditions where TORC1 kinase activity is undetectable. Metabolic flux and transcriptome analysis revealed that Kog1 controls SNF1-dependent carbon flux apportioning between glutamate/amino acid biosynthesis and gluconeogenesis. Kog1 regulates SNF1/AMPK activity and outputs and mediates a rapamycin-independent activation of the SNF1 targets Mig1 and Cat8. This enables effective glucose derepression, gluconeogenesis activation, and carbon allocation through different pathways. Therefore, Kog1 centrally regulates metabolic homeostasis and carbon utilization during nutrient limitation by managing SNF1 activity.

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