TNF-α-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-XL

J. J. Kim, S. B. Lee, J. K. Park, Y. D. Yoo

Research output: Contribution to journalArticlepeer-review

256 Citations (Scopus)


Reactive oxygen species (ROS) produced by tumor necrosis factor-α (TNF-α) have an important function in cell death by activating c-Jun N-terminal kinase. However, the exact mechanism of mitochondrial ROS production, after TNF-α 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-α-induced ROS production. In response to TNF-α, 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-α signaling and the mitochondria for ROS production that triggers TNF-α-mediated apoptosis, as well as a novel target in the development of anti-inflammatory agents that block the origin of ROS production.

Original languageEnglish
Pages (from-to)1420-1434
Number of pages15
JournalCell Death and Differentiation
Issue number9
Publication statusPublished - 2010 Sept


  • Bcl-X
  • ROS
  • Romo1
  • TNF-α
  • apoptosis
  • mitochondria

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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