Role of Mitochondrial Reactive Oxygen Species in the Activation of Cellular Signals, Molecules, and Function

  • Hiroko P. Indo
  • Clare L. Hawkins
  • Ikuo Nakanishi
  • Ken-ichiro Matsumoto
  • Hirofumi Matsui
  • Shigeaki Suenaga
  • Michael J. Davies
  • Daret K. St Clair
  • Toshihiko Ozawa
  • Hideyuki J. Majima
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 240)


Mitochondria are a major source of intracellular energy and reactive oxygen species in cells, but are also increasingly being recognized as a controller of cell death. Here, we review evidence of signal transduction control by mitochondrial superoxide generation via the nuclear factor-κB (NF-κB) and GATA signaling pathways. We have also reviewed the effects of ROS on the activation of MMP and HIF. There is significant evidence to support the hypothesis that mitochondrial superoxide can initiate signaling pathways following transport into the cytosol. In this study, we provide evidence of TATA signal transductions by mitochondrial superoxide. Oxidative phosphorylation via the electron transfer chain, glycolysis, and generation of superoxide from mitochondria could be important factors in regulating signal transduction, cellular homeostasis, and cell death.


Activation GATA HIF Mitochondria Mitochondrial ROS MMP MnSOD NF-κB Reactive oxygen species Signal transduction Superoxide 



This work was supported in part by a Grant-in-Aid for Scientific Research (C) (No. 22592093 to H.J.M.) and the Strategic Promotion Program for Basic Nuclear Research (to H.J.M.) of the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry (BRAIN) (to H.J.M.) by the Ministry of Agriculture, Forestry and Fisheries of Japan. M.J.D. gratefully acknowledges financial support from the Novo Nordisk Foundation (Laureate Research Grant NNF13OC0004294).

Conflict of Interest

No potential conflicts of interest were disclosed.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Hiroko P. Indo
    • 1
    • 2
    • 3
  • Clare L. Hawkins
    • 4
    • 5
  • Ikuo Nakanishi
    • 6
  • Ken-ichiro Matsumoto
    • 6
  • Hirofumi Matsui
    • 7
  • Shigeaki Suenaga
    • 1
  • Michael J. Davies
    • 8
  • Daret K. St Clair
    • 3
  • Toshihiko Ozawa
    • 9
  • Hideyuki J. Majima
    • 1
    • 2
  1. 1.Department of OncologyKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
  2. 2.Department of Space Environmental MedicineKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
  3. 3.Graduate Center of Toxicology and Markey Cancer CenterUniversity of Kentucky College of MedicineLexingtonUSA
  4. 4.The Heart Research InstituteNewtownAustralia
  5. 5.Sydney Medical SchoolUniversity of SydneySydneyAustralia
  6. 6.Quantitative RedOx Sensing Team (QRST), Department of Basic Medical Sciences for Radiation DamagesNational Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST)ChibaJapan
  7. 7.Division of Gastroenterology, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  8. 8.Department of Biomedical Sciences, Panum InstituteUniversity of CopenhagenCopenhagenDenmark
  9. 9.Division of Oxidative Stress ResearchShowa Pharmaceutical UniversityMachidaJapan

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