期刊
CELL DEATH AND DIFFERENTIATION
卷 17, 期 9, 页码 1420-1434出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2010.19
关键词
TNF-alpha; ROS; apoptosis; mitochondria; Romo1; Bcl-X-L
资金
- Korean Government (MEST) [FG06-2-20]
- Ministry for Health, Welfare & Family Affairs, Republic of Korea [A084537]
- Ministry of Education, Science and Technology [R01-2006-000-10113-0]
- MEST [R11-2005-017-04001-0]
- Korea Health Promotion Institute [A084537] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2003-02162, R01-2006-000-10113-0, 02-2006-00-011-00, R11-2005-017-04001-0, 2008-0057884] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Reactive oxygen species (ROS) produced by tumor necrosis factor-a (TNF-alpha) have an important function in cell death by activating c-Jun N-terminal kinase. However, the exact mechanism of mitochondrial ROS production, after TNF-alpha stimulation, is not clearly understood. In this study, we determined that ROS modulator 1 (Romo1) and B-cell lymphoma-extra large (Bcl-X-L) are directly associated with TNF-alpha-induced ROS production. In response to TNF-alpha, TNF complex II, which consists of receptor-interacting protein 1, TNF receptor-associated protein with death domain, TNF receptor-associated factor 2, Fas-associated death domain protein, and pro-caspase-8, binds to the C-terminus of Romo1 located in the mitochondria. Concurrently, Romo1 recruits Bcl-X-L to reduce the mitochondrial membrane potential, resulting in ROS production and apoptotic cell death. On the basis of these results, we suggest that Romo1 is a molecular bridge between TNF-alpha signaling and the mitochondria for ROS production that triggers TNF-alpha-mediated apoptosis, as well as a novel target in the development of anti-inflammatory agents that block the origin of ROS production. Cell Death and Differentiation (2010) 17, 1420-1434; doi:10.1038/cdd.2010.19; published online 5 March 2010
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