Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response

R. Lall, S. Ganapathy, M. Yang, S. Xiao, T. Xu, H. Su, M. Shadfan, J. M. Asara, C. S. Ha, I. Ben-Sahra, B. D. Manning, J. B. Little, Z. M. Yuan

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Because of insufficient understanding of the molecular effects of low levels of radiation exposure, there is a great uncertainty regarding its health risks. We report here that treatment of normal human cells with low-dose radiation induces a metabolic shift from oxidative phosphorylation to aerobic glycolysis resulting in increased radiation resistance. This metabolic change is highlighted by upregulation of genes encoding glucose transporters and enzymes of glycolysis and the oxidative pentose phosphate pathway, concomitant with downregulation of mitochondrial genes, with corresponding changes in metabolic flux through these pathways. Mechanistically, the metabolic reprogramming depends on HIF1, which is induced specifically by low-dose irradiation linking the metabolic pathway with cellular radiation dose response. Increased glucose flux and radiation resistance from low-dose irradiation are also observed systemically in mice. This highly sensitive metabolic response to low-dose radiation has important implications in understanding and assessing the health risks of radiation exposure.

Original languageEnglish (US)
Pages (from-to)836-844
Number of pages9
JournalCell Death and Differentiation
Volume21
Issue number5
DOIs
StatePublished - May 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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