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.