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Published on: June 12, 2017
Methionine inhibits autophagy and promotes growth by inducing the SAM-responsive methylation of PP2A
Benjamin M Sutter1, Xi Wu, Sunil Laxman
1Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA.
Abstract:
Autophagy is a process of cellular self-digestion induced by various forms of starvation. Although nitrogen deficit is a common trigger, some yeast cells induce autophagy upon switch from a rich to minimal media without nitrogen starvation. We show that the amino acid methionine is sufficient to inhibit such non-nitrogen-starvation (NNS)-induced autophagy. Methionine boosts synthesis of the methyl donor, S-adenosylmethionine (SAM). SAM inhibits autophagy and promotes growth through the action of the methyltransferase Ppm1p, which modifies the catalytic subunit of PP2A in tune with SAM levels. Methylated PP2A promotes dephosphorylation of Npr2p, a component of a conserved complex that regulates NNS autophagy and other growth-related processes. Thus, methionine and SAM levels represent a critical gauge of amino acid availability that is sensed via the methylation of PP2A to reciprocally regulate cell growth and autophagy.
Insights
Methionine inhibits yeast autophagy by boosting S-adenosylmethionine (SAM) synthesis. SAM activates methyltransferase Ppm1p, which modifies PP2A to regulate cell growth and autophagy based on amino acid availability.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Autophagy is cellular self-digestion, typically triggered by starvation.
- Yeast can initiate autophagy even without nitrogen starvation when switching media.
- Understanding triggers for non-nitrogen-starvation (NNS)-induced autophagy is crucial for cellular regulation.
Purpose of the Study:
- To investigate the role of methionine in regulating non-nitrogen-starvation (NNS)-induced autophagy in yeast.
- To elucidate the molecular mechanism by which methionine influences autophagy.
- To identify key proteins and pathways involved in sensing amino acid availability for autophagy control.
Main Methods:
- Yeast cell culture under varying media conditions.
- Measurement of autophagy markers.
- Analysis of S-adenosylmethionine (SAM) levels.
- Enzyme activity assays for Ppm1p and PP2A.
- Phosphorylation analysis of Npr2p.
Main Results:
- Methionine was identified as sufficient to inhibit NNS-induced autophagy.
- Methionine increases S-adenosylmethionine (SAM) levels, a key methyl donor.
- SAM-dependent methylation of PP2A by Ppm1p was observed.
- Methylated PP2A dephosphorylates Npr2p, regulating autophagy and growth.
Conclusions:
- Methionine and SAM levels act as critical sensors of amino acid availability.
- The methylation of PP2A by Ppm1p is a key mechanism linking SAM levels to NNS autophagy.
- This pathway reciprocally regulates yeast cell growth and autophagy in response to nutrient status.
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