Yeast DJ-1 superfamily members are required for diauxic-shift reprogramming and cell survival in stationary phase.
The yeast Hsp31 minifamily proteins (Hsp31, Hsp32, Hsp33, Hsp34) belong to the highly conserved DJ-1 superfamily. The human DJ-1 protein is associated with cancer and neurodegenerative disorders, such as Parkinson disease. However, the precise function of human and yeast DJ-1 proteins is unclear. Here we show that the yeast DJ-1 homologs have a role in diauxic-shift (DS), characterized by metabolic reprogramming because of glucose limitation. We find that the Hsp31 genes are strongly induced in DS and in stationary phase (SP), and that deletion of these genes reduces chronological lifespan, impairs transcriptional reprogramming at DS, and impairs the acquisition of several typical characteristics of SP, including autophagy induction. In addition, under carbon starvation, the HSP31 family gene-deletion strains display impaired autophagy, disrupted target of rapamycin complex 1 (TORC1) localization to P-bodies, and caused abnormal TORC1-mediated Atg13 phosphorylation. Repression of TORC1 by rapamycin in the gene-deletion strains completely reversed their sensitivity to heat shock. Taken together, our data indicate that Hsp31 minifamily is required for DS reprogramming and cell survival in SP, and plays a role upstream of TORC1. The enhanced understanding of the cellular function of these genes sheds light into the biological role of other members of the superfamily, including DJ-1, which is an attractive target for therapeutic intervention in cancer and in Parkinson disease.
Instituto de Medicina Molecular, 1649-028 Lisbon, Portugal;Department of Genetics, University of Leicester, Leicester LE1 7RH, United Kingdom;
Leonor
L
Miller-Fleming
Instituto de Medicina Molecular, 1649-028 Lisbon, Portugal;
Pedro
P
Antas
Instituto de Medicina Molecular, 1649-028 Lisbon, Portugal;
Teresa Faria
TF
Pais
Department of Genetics, University of Leicester, Leicester LE1 7RH, United Kingdom;Systems Toxicology Group, Medical Research Council Toxicology Unit, University of Leicester, LE1 9HN Leicester, United Kingdom;
Joshua L
JL
Smalley
Department of Genetics, University of Leicester, Leicester LE1 7RH, United Kingdom; fg36@le.ac.uk touteiro@gmail.com.
Flaviano
F
Giorgini
Instituto de Medicina Molecular, 1649-028 Lisbon, Portugal;Instituto de Fisiologia, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal; andDepartment of Neurodegeneration and Restorative Research, University Medical Center Göttingen, 37073 Göttingen, Germany fg36@le.ac.uk touteiro@gmail.com.
Tiago Fleming
TF
Outeiro
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000235:genetics; D002244:Carbon / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
D006360:Heat-Shock Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; D002244:Carbon; D000626:Aminopeptidases; C556680:Hsp33 protein, S cerevisiae; C496117:HSP31 protein, S cerevisiae; D005947:Glucose