Impaired oxidative phosphorylation regulates necroptosis in human lung epithelial cells

Michael Jakun Koo, Kristen T. Rooney, Mary E. Choi, Stefan W. Ryter, Augustine M.K. Choi, Jong Seok Moon

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Abstract Cellular metabolism can impact cell life or death outcomes. While metabolic dysfunction has been linked to cell death, the mechanisms by which metabolic dysfunction regulates the cell death mode called necroptosis remain unclear. Our study demonstrates that mitochondrial oxidative phosphorylation (OXPHOS) activates programmed necrotic cell death (necroptosis) in human lung epithelial cells. Inhibition of mitochondrial respiration and ATP synthesis induced the phosphorylation of mixed lineage kinase domain-like protein (MLKL) and necroptotic cell death. Furthermore, we demonstrate that the activation of AMP-activated protein kinase (AMPK), resulting from impaired mitochondrial OXPHOS, regulates necroptotic cell death. These results suggest that impaired mitochondrial OXPHOS contributes to necroptosis in human lung epithelial cells.

Original languageEnglish (US)
Article number34265
Pages (from-to)875-880
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume464
Issue number3
DOIs
StatePublished - Aug 7 2015

Keywords

  • AMPK
  • Mitochondria
  • Necroptosis
  • Oxidative phosphorylation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Impaired oxidative phosphorylation regulates necroptosis in human lung epithelial cells'. Together they form a unique fingerprint.

Cite this