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Cited by 103Mitochondrial Function and PathologyIon channel regulation and functionATP Synthase and ATPases Research

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Reverse electron flow-induced ROS production is attenuated by activation of mitochondrial Ca2+-sensitive K+ channels

Heinen, André, Aldakkak, Mohammed, Stowe, David F., Rhodes, Samhita S., Riess, Matthias L., Varadarajan, Srinivasan G., Camara, Amadou K. S.·2007·American Journal of Physiology-Heart and Circulatory Physiology
DOI 10.1152/ajpheart.00198.2007
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Abstract

Mitochondria generate reactive oxygen species (ROS) dependent on substrate conditions, O 2 concentration, redox state, and activity of the mitochondrial complexes. It is well known that the FADH 2-linked substrate succinate induces reverse electron flow to complex I of the electron transport chain and that this process generates superoxide (O 2•−); these effects are blocked by the complex I blocker rotenone. We demonstrated recently that succinate + rotenone-dependent H 2 O 2 production in isolated mitochondria increased mildly on activation of the putative big mitochondrial Ca 2+-sensitive K+ channel (mtBK Ca) by low concentrations of 1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2 H-benzimidazol-2-one (NS-1619). In the present study we examined effects of NS-1619 on mitochondrial O 2 consumption, membrane potential (ΔΨ m), H 2 O 2 release rates, and redox state in isolated guinea pig heart mitochondria respiring on succinate but without rotenone. NS-1619 (30 μM) increased state 2 and state 4 respiration by 26 ± 4% and 14 ± 4%, respectively; this increase was abolished by the BK Ca channel blocker paxilline (5 μM). Paxilline alone had no effect on respiration. NS-1619 did not alter ΔΨ m or redox state but decreased H 2 O 2 production by 73% vs. control; this effect was incompletely inhibited by paxilline. We conclude that under substrate conditions that allow reverse electron flow, matrix K+ influx through mtBK Ca channels reduces mitochondrial H 2 O 2 production by accelerating forward electron flow. Our prior study showed that NS-1619 induced an increase in H 2 O 2 production with blocked reverse electron flow. The present results suggest that NS-1619-induced matrix K+ influx increases forward electron flow despite the high reverse electron flow, and emphasize the importance of substrate conditions on interpretation of effects on mitochondrial bioenergetics.

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Crossref · 10.1152/ajpheart.00198.2007

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Metadata

Authors
Heinen, A., Aldakkak, M., Stowe, D. F., Rhodes, S. S., Riess, M. L., Varadarajan, S. G., & Camara, A. K. S.
Affiliations
Medical College of Wisconsin (US)
ORCID
Venue
American Journal of Physiology-Heart and Circulatory Physiology
Publisher
American Physiological Society
Published
2007-09
Volume
293
Issue
3
Pages
H1400-H1407
ISSN
  • 0363-6135 (ISSN-L)
  • 1522-1539
DOI
10.1152/ajpheart.00198.2007
OpenAlex
W2142188717
Cited by
103
References
42
Citations by year
2026: 3 · 2025: 5 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 7 · 2015: 7 · 2014: 7 · 2013: 7 · 2012: 10
FWCI
1.72
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (K01HL073246, K01-HL-73246-02)
  • National Eye Institute (P30 EY01931, P30EY001931)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
Keywords
reverse electron flow, reactive oxygen species, NS1619, paxilline, superoxide, hydrogen peroxide production, complex I, electron transport chain, mitochondrial respiration, heart mitochondria, substrate conditions
MeSH terms
Animals, Benzimidazoles, Guinea Pigs, Hydrogen Peroxide, Indoles, Mitochondria, Heart, Oxidation-Reduction, Potassium, Reactive Oxygen Species, Cell Respiration, Potassium Channels, Calcium-Activated, Potassium Channel Blockers, Membrane Potential, Mitochondrial

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