title: Methionine inhibits autophagy and promotes growth by inducing the SAM-responsive methylation of PP2A.
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.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Sutter
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.forename: Sunil
authors.initials: S
authors.lastname: Laxman
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Tu
mesh_terms: D001343:Autophagy; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008715:Methionine / Q000378:metabolism*; D008745:Methylation; D011496:Protein Methyltransferases / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C092275:NPR2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012436:S-Adenosylmethionine; D008715:Methionine; C442645:Ppm1 protein, S cerevisiae; D011496:Protein Methyltransferases; D054648:Protein Phosphatase 2