The methanol sensor Wsc1 and MAPK Mpk1 suppress degradation of methanol-induced peroxisomes in methylotrophic yeast

In nature, methanol is produced during the hydrolysis of pectin in plant cell walls. Methanol on plant leaves shows circadian dynamics, to which methanol-utilizing phyllosphere microorganisms adapt. In the methylotrophic yeast Komagataella phaffii (Kp; also known as Pichia pastoris), the plasma membrane protein KpWsc1 senses environmental methanol concentrations and transmits this information to induce the expression of genes for methanol metabolism and the formation of huge peroxisomes. In this study, we show that KpWsc1 and its downstream MAPK, KpMpk1, negatively regulate pexophagy in the presence of methanol concentrations greater than 0.15%. Although KpMpk1 was not necessary for expression of methanol-inducible genes and peroxisome biogenesis, KpMpk1, the transcription factor KpRlm1 and phosphatases were found to suppress pexophagy by controlling phosphorylation of KpAtg30, the key factor in regulation of pexophagy. We reveal at the molecular level how the single methanol sensor KpWsc1 commits the cell to peroxisome synthesis and degradation according to the methanol concentration, and we discuss the physiological significance of regulating pexophagy for survival in the phyllosphere. This article has an associated First Person interview with Shin Ohsawa, joint first author of the paper.