File(s) under permanent embargo
Reason: This item is currently closed access.
Yeast DJ-1 superfamily members are required for diauxic-shift reprogramming and cell survival in stationary phase
journal contributionposted on 2016-04-15, 10:39 authored by L. Miller-Fleming, P. Antas, T. F. Pais, J. L. Smalley, Flaviano Giorgini, T. F. Outeiro
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.
CitationProceedings of the National Academy of Sciences, 2014, 111 (19), pp. 7012-7017
Author affiliation/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Department of Genetics
- VoR (Version of Record)
Published inProceedings of the National Academy of Sciences
PublisherNational Academy of Sciences
NotesThe file associated with this record is under permanent embargo by the publisher. Please use the links above where the Published version is freely available.