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Impaired oxidative phosphorylation regulates necroptosis in human lung epithelial cells

Author:
Koo, Michael Jakun, Rooney, Kristen T., Choi, Mary E., Ryter, Stefan W., Choi, Augustine M.K., Moon, Jong-Seok
Source:
Biochemical and biophysical research communications 2015 v.464 pp. 875-880
ISSN:
0006-291X
Subject:
AMP-activated protein kinase, adenosine triphosphate, cell death, death, epithelial cells, humans, mitochondria, oxidative phosphorylation
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.
Agid:
5332241