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RIP3-Dependent Accumulation of Mitochondrial Superoxide Anions in TNF-α-Induced Necroptosis
- Title
- RIP3-Dependent Accumulation of Mitochondrial Superoxide Anions in TNF-α-Induced Necroptosis
- Authors
- Lee J.; Lee S.; Min S.; Kang S.W.
- Ewha Authors
- 강상원; 민성춘
- SCOPUS Author ID
- 강상원; 민성춘
- Issue Date
- 2022
- Journal Title
- Molecules and Cells
- ISSN
- 1016-8478
- Citation
- Molecules and Cells vol. 45, no. 4, pp. 193 - 201
- Keywords
- NADPH oxidase; necroptosis; superoxide anion; tumor necrosis factor-α
- Publisher
- Korean Society for Molecular and Cellular Biology
- Indexed
- SCIE; SCOPUS; KCI
- Document Type
- Article
- 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. © The Korean Society for Molecular and Cellular Biology.
- DOI
- 10.14348/molcells.2021.0260
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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