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http://dx.doi.org/10.14348/molcells.2021.0260

RIP3-Dependent Accumulation of Mitochondrial Superoxide Anions in TNF-α-Induced Necroptosis  

Lee, Jiyoung (Department of Life Science, College of Natural Science, Ewha Womans University)
Lee, Sunmi (Department of Life Science, College of Natural Science, Ewha Womans University)
Min, Seongchun (Department of Life Science, College of Natural Science, Ewha Womans University)
Kang, Sang Won (Department of Life Science, College of Natural Science, Ewha Womans University)
Publication Information
Molecules and Cells / v.45, no.4, 2022 , pp. 193-201 More about this Journal
Abstract
Excessive production of reactive oxygen species (ROS) is a key phenomenon in tumor necrosis factor (TNF)-α-induced cell death. However, the role of ROS in necroptosis remains mostly elusive. In this study, we show that TNF-α induces the mitochondrial accumulation of superoxide anions, not H2O2, in cancer cells undergoing necroptosis. TNF-α-induced mitochondrial superoxide anions production is strictly RIP3 expression-dependent. Unexpectedly, TNF-α stimulates NADPH oxidase (NOX), not mitochondrial energy metabolism, to activate superoxide production in the RIP3-positive cancer cells. In parallel, mitochondrial superoxide-metabolizing enzymes, such as manganese-superoxide dismutase (SOD2) and peroxiredoxin III, are not involved in the superoxide accumulation. Mitochondrial-targeted superoxide scavengers and a NOX inhibitor eliminate the accumulated superoxide without affecting TNF-α-induced necroptosis. Therefore, our study provides the first evidence that mitochondrial superoxide accumulation is a consequence of necroptosis.
Keywords
NADPH oxidase; necroptosis; superoxide anion; tumor necrosis factor-${\alpha}$;
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Times Cited By KSCI : 4  (Citation Analysis)
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