A Possible Site of Superoxide Generation in the Complex I Segment of Rat Heart Mitochondria

Ohnishi, S. Tsuyoshi; Ohnishi, Tomoko; Muranaka, Shikibu; Fujita, Hirofumi; Kimura, Hiroko; Uemura, Koichi; Yoshida, Ken-ichi; Utsumi, Kozo

doi:10.1007/s10863-005-4117-y

Cited by 123Mitochondrial Function and PathologyCoenzyme Q10 studies and effectsRedox biology and oxidative stress

A Possible Site of Superoxide Generation in the Complex I Segment of Rat Heart Mitochondria

Ohnishi, S. Tsuyoshi, Ohnishi, Tomoko, Muranaka, Shikibu, Fujita, Hirofumi, Kimura, Hiroko, Uemura, Koichi, Yoshida, Ken-ichi, Utsumi, Kozo·2005·Journal of Bioenergetics and Biomembranes

DOI 10.1007/s10863-005-4117-y

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Abstract

We searched for possible sites of superoxide generation in the complex I segment of the respiratory chain by studying both forward and reverse electron transfer reactions in isolated rat heart mitochondria. Superoxide production was monitored by measuring the release of hydrogen peroxide from mitochondria with a fluorescence spectrophotometer using the Amplex red/horseradish peroxidase system. In the forward electron transfer, a slow superoxide production in the presence of glutamate and malate was enhanced by both rotenone and piericidin A (specific inhibitors at the end of the complex I respiratory chain). Both diphenileneiodonium and ethoxyformic anhydride (inhibitors for respiratory components located upstream of the respiratory chain) inhibited the enhancement by rotenone and piericidin A. In contrast, in reverse electron transfer driven by ATP, both diphenileneiodonium and ethoxyformic anhydride enhanced the superoxide production. Piericidin A also increased superoxide production. Rotenone increased it only in the presence of piericidin A. Our results suggest that the major site of superoxide generation is not flavin, but protein-associated ubisemiquinones which are spin-coupled with iron-sulfur cluster N2.

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Although nonmitochondrial sources of ROS exist during ischemia, the majority of ROS are likely derived from the mitochondrial respiratory complexes.
“Although nonmitochondrial sources of ROS exist during ischemia [e.g., NAD(P)H oxidase (141, 188, 328) and xanthine oxidase (25) in vasculature], the majority of ROS are likely derived from the mitochondrial respiratory complexes, as shown by the damage to respiratory complexes (212, 213, 245) and the effect of mitochondrial inhibitors (5, 28, 71, 81–86).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [245]

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Authors: Ohnishi, S. T., Ohnishi, T., Muranaka, S., Fujita, H., Kimura, H., Uemura, K., Yoshida, K.-I., & Utsumi, K.
Affiliations: Kurashiki Medical Center (JP)
Juntendo University (JP)
The University of Tokyo (JP)
Corresponding author: Ohnishi, S. Tsuyoshi
ORCID: Fujita, Hirofumi
Kimura, Hiroko
Venue: Journal of Bioenergetics and Biomembranes
Publisher: Springer Science and Business Media LLC
Published: 2005-02
Volume: 37
Issue: 1
Pages: 1-15
ISSN: 0145-479X (ISSN-L)
1573-6881
DOI: 10.1007/s10863-005-4117-y
OpenAlex: W2044142994
Cited by: 123
References: 94
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2021: 5 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 8 · 2015: 2 · 2014: 9 · 2013: 5 · 2012: 8
FWCI: 4.39
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Journal of Bioenergetics and Biomembranes (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (GM30736, R01GM030736)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords: superoxide production, complex I, electron transport chain, heart mitochondria, reverse electron transfer, rotenone, piericidin A, hydrogen peroxide release, flavin, ubiquinol, spin-spin coupling, oxidative stress
MeSH terms: Strobilurins, Animals, Electron Transport, Fatty Acids, Unsaturated, Kinetics, Methacrylates, Mitochondria, Heart, Models, Biological, Superoxides, Electron Transport Complex III, Electron Transport Complex I, Rats

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A Possible Site of Superoxide Generation in the Complex I Segment of Rat Heart Mitochondria

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