Glucocorticoid receptor isoforms direct distinct mitochondrial programs to regulate ATP production

Research output: Contribution to journalArticle

  • External authors:
  • Toryn Poolman
  • Andrew Williamson
  • Zichen Wang
  • Neil R. Clark
  • Avi Ma’ayan

Abstract

The glucocorticoid receptor (GR), a nuclear receptor and major drug target, has a highly conserved minor splice variant, GRγ, which differs by a single arginine within the DNA binding domain. GRγ, which comprises 10% of all GR transcripts, is constitutively expressed and tightly conserved through mammalian evolution, suggesting an important non-redundant role. However, to date no specific role for GRγ has been reported. We discovered significant differences in subcellular localisation, and nuclear-cytoplasmic shuttling in response to ligand. In addition the GRγ transcriptome and protein interactome was distinct, and with a gene ontology signal for mitochondrial regulation which was confirmed using Seahorse technology. We propose that evolutionary conservation of the single additional arginine in GRγ is driven by a distinct, non-redundant functional profile, including regulation of mitochondrial function.

Bibliographical metadata

Original languageEnglish
JournalScientific Reports
DOIs
StatePublished - 26 May 2016