Related Experiment Video

Updated: Aug 5, 2025

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

14.1K

Evidence of Nrf2/Keap1 Signaling Regulation by Mitochodria-Generated Reactive Oxygen Species in RGK1 Cells

Hiroko P Indo1,2, Daisuke Masuda3,4, Sompong Sriburee1,5

  • 1Department of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.

Biomolecules
|March 29, 2023
PubMed

Insights

Mitochondrial reactive oxygen species (mtROS) signal to the nucleus. This study demonstrates that increased mtROS in RGK1 cells activate nuclear signaling proteins, suggesting mtROS influence cellular responses.

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Oxidative Stress

Background:

  • Mitochondrial electron transport chain (ETC) generates reactive oxygen species (ROS).
  • Mitochondrial ROS (mtROS) were previously shown to induce apoptosis.
  • The translocation of mtROS to initiate nuclear signaling is hypothesized.

Purpose of the Study:

  • To investigate the role of mtROS in initiating cellular signals within the nucleus.
  • To assess changes in nuclear signaling proteins in response to varying mtROS levels.
  • To confirm the extramitochondrial function of mtROS.

Main Methods:

  • Comparison of two cell lines (RGK1 and RGM1) with differing mtROS production.
  • Immunocytochemistry staining to analyze protein expression levels.
  • MnSOD transfection in RGK1 cells to modulate mtROS levels.

Main Results:

  • RGK1 cells exhibited higher levels of Nrf2, Keap1, HO-1, HO-2, MnSOD, GCL, GST, NQO1, and GATA factors compared to RGM1 cells.
  • Transfection of MnSOD in RGK1 cells led to a decrease in these signaling proteins.
  • These findings suggest a correlation between mtROS levels and nuclear signaling pathways.

Conclusions:

  • Mitochondrial ROS (mtROS) play a significant role in initiating cellular signals within the nucleus.
  • The observed changes in protein expression confirm the extramitochondrial signaling capacity of mtROS.
  • Targeting mtROS could offer therapeutic strategies for diseases involving oxidative stress.
Keywords:
Nrf2/Keap1cell signalinggastric mucosal cellsmitochondriareactive oxygen speciessignal transductiontumorized cells

More Related Videos

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases08:57

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases

Published on: February 24, 2018

10.1K
Ratiometric Biosensors that Measure Mitochondrial Redox State and ATP in Living Yeast Cells12:22

Ratiometric Biosensors that Measure Mitochondrial Redox State and ATP in Living Yeast Cells

Published on: July 22, 2013

21.1K

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.7K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
14.7K
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
11.7K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.7K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
79.1K