Mitochondria Play Essential Roles in Intracellular Protection against Oxidative Stress—Which Molecules among the ROS Generated in the Mitochondria Can Escape the Mitochondria and Contribute to Signal Activation in Cytosol?

Daisuke Masuda, Ikuo Nakanishi*, Kei Ohkubo, Hiromu Ito, Ken Ichiro Matsumoto, Hiroshi Ichikawa, Moragot Chatatikun, Wiyada Kwanhian Klangbud, Manas Kotepui, Motoki Imai, Fumitaka Kawakami, Makoto Kubo, Hirofumi Matsui, Jitbanjong Tangpong, Takafumi Ichikawa, Toshihiko Ozawa, Hsiu Chuan Yen, Daret K. St Clair, Hiroko P. Indo*, Hideyuki J. Majima*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

10 Scopus citations

Abstract

Questions about which reactive oxygen species (ROS) or reactive nitrogen species (RNS) can escape from the mitochondria and activate signals must be addressed. In this study, two parameters, the calculated dipole moment (debye, D) and permeability coefficient (Pm) (cm s−1), are listed for hydrogen peroxide (H2O2), hydroxyl radical (•OH), superoxide (O2•−), hydroperoxyl radical (HO2•), nitric oxide (•NO), nitrogen dioxide (•NO2), peroxynitrite (ONOO), and peroxynitrous acid (ONOOH) in comparison to those for water (H2O). O2•− is generated from the mitochondrial electron transport chain (ETC), and several other ROS and RNS can be generated subsequently. The candidates which pass through the mitochondrial membrane include ROS with a small number of dipoles, i.e., H2O2, HO2•, ONOOH, •OH, and •NO. The results show that the dipole moment of •NO2 is 0.35 D, indicating permeability; however, •NO2 can be eliminated quickly. The dipole moments of •OH (1.67 D) and ONOOH (1.77 D) indicate that they might be permeable. This study also suggests that the mitochondria play a central role in protecting against further oxidative stress in cells. The amounts, the long half-life, the diffusion distance, the Pm, the one-electron reduction potential, the pKa, and the rate constants for the reaction with ascorbate and glutathione are listed for various ROS/RNS, •OH, singlet oxygen (1O2), H2O2, O2•−, HO2•, •NO, •NO2, ONOO, and ONOOH, and compared with those for H2O and oxygen (O2). Molecules with negative electrical charges cannot directly diffuse through the phospholipid bilayer of the mitochondrial membranes. Short-lived molecules, such as •OH, would be difficult to contribute to intracellular signaling. Finally, HO2• and ONOOH were selected as candidates for the ROS/RNS that pass through the mitochondrial membrane.

Original languageEnglish
Article number128
JournalBiomolecules
Volume14
Issue number1
DOIs
StatePublished - 19 01 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

  • cell signaling
  • dipole moment
  • mitochondria
  • Nrf2/Keap1
  • reactive oxygen species
  • signal transduction
  • Oxygen
  • Reactive Oxygen Species
  • Hydrogen Peroxide/pharmacology
  • Oxidative Stress
  • Peroxynitrous Acid
  • Nitric Oxide
  • Cytosol
  • Mitochondria
  • Nitrogen Dioxide

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