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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

TNF-alpha-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-X(L)

J J Kim1, S B Lee, J K Park

  • 1Korea University College of Medicine, Korea University, Seoul, Republic of Korea.

Cell Death and Differentiation
|March 6, 2010
PubMed

Insights

Tumor necrosis factor-alpha (TNF-alpha) triggers cell death via mitochondrial reactive oxygen species (ROS). This study identifies ROS modulator 1 (Romo1) as a key mitochondrial protein linking TNF-alpha signaling to ROS production and apoptosis.

Area of Science:

  • Cellular Biology
  • Biochemistry
  • Immunology

Background:

  • Reactive oxygen species (ROS) play a critical role in TNF-alpha-mediated apoptosis by activating c-Jun N-terminal kinase.
  • The precise mechanism of mitochondrial ROS generation following TNF-alpha stimulation remains incompletely elucidated.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying TNF-alpha-induced mitochondrial ROS production.
  • To identify key proteins involved in the signaling pathway linking TNF-alpha to mitochondrial ROS generation and subsequent apoptosis.

Main Methods:

  • The study involved analyzing the interaction of TNF complex II components with mitochondrial proteins.
  • Experiments focused on the role of ROS modulator 1 (Romo1) and B-cell lymphoma-extra large (Bcl-X(L)) in TNF-alpha signaling.
  • Mitochondrial membrane potential and ROS production were measured following TNF-alpha stimulation.

Main Results:

  • Romo1 and Bcl-X(L) were found to be directly associated with TNF-alpha-induced ROS production.
  • TNF complex II binds to the C-terminus of Romo1 in the mitochondria upon TNF-alpha stimulation.
  • Romo1 recruits Bcl-X(L), leading to reduced mitochondrial membrane potential, ROS production, and apoptotic cell death.

Conclusions:

  • Romo1 acts as a molecular bridge connecting TNF-alpha signaling to mitochondrial ROS production.
  • This pathway culminates in TNF-alpha-mediated apoptosis.
  • Romo1 represents a potential therapeutic target for developing anti-inflammatory agents that inhibit ROS production at its source.

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