Disrupted lipid homeostasis in the absence of the transcriptional activator mga2 results in a failure to activate SREBPs in Schizosaccharomyces pombe

ABSTRACT: The sre1 pathway senses molecular oxygen in the fission yeast, Schizosaccharomyces pombe. When oxygen becomes limiting, Sre1 is trafficked from the ER to the Golgi where it is cleaved through the actions of the 5-member Dsc E3 ligase complex. The released N-terminus then upregulates genes required for adaptation to hypoxia. Although the sre1 pathway is responsible for regulating a majority of the genes required for hypoxic growth, it is evident that other regulatory genes are involved in this response. To identify novel regulators of adaptation to hypoxia, we screened the S. pombe nonessential haploid deletion collection. This genome wide screen identified nine genes required for production of the membrane-bound transcription factor Sre1N. The characterization of one of these, the S. pombe transcriptional activator mga2, is presented. mga2 is the homolog of SPT23 and MGA2 in S. cerevisiae. In S. cerevisiae SPT23 and MGA2 regulate the transcription of genes involved in lipid metabolism, including the delta-9 fatty acid desaturase, OLE1. We show S. pombe mga2 also regulates lipid metabolism, and that in the absence of mga2, the lipidome is disrupted. Supplementation with unsaturated fatty acids rescued Sre1 cleavage in mga2Δ cells. However, mga2 is not simply required for activation of Sre1 as mga2Δ cells have a normoxia growth defect that is unrelated to Srel activity. Loss of mga2 results in aberrant Dsc1 glycosylation, suggesting that the Dsc complex is not properly localized to the Golgi. These results establish unsaturated fatty acids as a regulator of the SREBP pathway in fission yeast.

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE60544 | GEO | 2016/04/06

SECONDARY ACCESSION(S): PRJNA258519

REPOSITORIES: GEO