The regulation of TORC1 pathway by the yeast chaperones Hsp31 is mediated by SFP1 and affects proteasomal activity

摘要

The Saccharomyces cerevisiae heat shock proteins Hsp31-34 are members of DJ-1/ThiJ/Pfpl superfamily that includes human DJ-1 (Park7), a protein involved in heritable Parkinsonism. Although, homologs of these proteins can be found in most organisms their functions are unclear. We have carried out a quantitative proteomics analysis of yeast cells devoid of the whole set of Hsp31 family of proteins, as a model of Parkinson Disease (PD), under conditions of glucose availability and starvation. The protein profile indicates a constitutive activation of the enzyme TORC1 that makes the cells more sensitive to stress conditions. TORC1 activation prevents the cells from diauxic shift and entry into the stationary phase inducing cell death. Sfp1 stays at the helm among the several transcription factors governing the cell adaptation to Hsp31-34 deficiency. We show that Sfp1 remains mainly in the nucleus likely releasing TORC1 from inhibition by cytosolic Sfp1. Impairment of glycolysis leads to increased levels of methylglyoxal and accumulation of glycated proteins. We also show an increase in proteasome subunits in the Hsp31-34 mutant, under the control of Rpn4 transcription factor. This increase is abnormally accompanied by a decrease in proteasomal activity which could lead to accumulation of aberrant proteins and contributing to cell death.