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
Affiliations
Daisuke Masuda
Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Kagoshima, Japan
Ikuo Nakanishi
Quantum RedOx Chemistry Team, Institute for Quantum Life Science (iQLS), Quantum Life and Medical Science Directorate (QLMS), National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
Kei Ohkubo
Institute for Advanced Co-Creation Studies, Open and Transdisciplinary Research Initiatives, Osaka University, Suita 565-0871, Japan
Hiromu Ito
Quantum RedOx Chemistry Team, Institute for Quantum Life Science (iQLS), Quantum Life and Medical Science Directorate (QLMS), National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
Ken-ichiro Matsumoto
Quantitative RedOx Sensing Group, Department of Radiation Regulatory Science Research, Institute for Radiological Science (NIRS), Quantum Life and Medical Science Directorate (QLMS), National Institutes for Quantum Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan
Hiroshi Ichikawa
Department of Medical Life Systems, Graduate School of Life and Medical Sciences, Doshisha University, Kyoto 610-0394, Kyoto, Japan
Moragot Chatatikun
School of Allied Health Sciences, Walailak University, Thasala, Nakhon Si Thammarat 80161, Thailand
Wiyada Kwanhian Klangbud
School of Allied Health Sciences, Walailak University, Thasala, Nakhon Si Thammarat 80161, Thailand
Manas Kotepui
School of Allied Health Sciences, Walailak University, Thasala, Nakhon Si Thammarat 80161, Thailand
Motoki Imai
Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Kanagawa, Japan
Fumitaka Kawakami
Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Kanagawa, Japan
Makoto Kubo
Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Kanagawa, Japan
Hirofumi Matsui
Division of Gastroenterology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
Jitbanjong Tangpong
School of Allied Health Sciences, Walailak University, Thasala, Nakhon Si Thammarat 80161, Thailand
Takafumi Ichikawa
Regenerative Medicine and Cell Design Research Facility, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Kanagawa, Japan
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Daret K. St Clair
Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
Hiroko P. Indo
Department of Maxillofacial Radiology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Kagoshima, Japan
Hideyuki J. Majima
Department of Space Environmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Kagoshima, Japan
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.
