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Cited by 235Mitochondrial Function and PathologyRedox biology and oxidative stressNonlinear Dynamics and Pattern Formation

The DOI matches its Crossref record; 60 of the 61 references it cites were found in a registry or an index.

A Mitochondrial Oscillator Dependent on Reactive Oxygen Species

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Cortassa, Sonia, Aon, Miguel A., Winslow, Raimond L., O’Rourke, Brian·2004·Biophysical Journal
DOI 10.1529/biophysj.104.041749PMC PMC1304608
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Abstract

We describe a unique mitochondrial oscillator that depends on oxidative phosphorylation, reactive oxygen species (ROS), and mitochondrial inner membrane ion channels. Cell-wide synchronized oscillations in mitochondrial membrane potential (Delta Psi(m)), NADH, and ROS production have been recently described in isolated cardiomyocytes, and we have hypothesized that the balance between superoxide anion efflux through inner membrane anion channels and the intracellular ROS scavenging capacity play a key role in the oscillatory mechanism. Here, we formally test the hypothesis using a computational model of mitochondrial energetics and Ca(2+) handling including mitochondrial ROS production, cytoplasmic ROS scavenging, and ROS activation of inner membrane anion flux. The mathematical model reproduces the period and phase of the observed oscillations in Delta Psi(m), NADH, and ROS. Moreover, we experimentally verify model predictions that the period of the oscillator can be modulated by altering the concentration of ROS scavengers or the rate of oxidative phosphorylation, and that the redox state of the glutathione pool oscillates. In addition to its role in cellular dysfunction during metabolic stress, the period of the oscillator can be shown to span a wide range, from milliseconds to hours, suggesting that it may also be a mechanism for physiological timekeeping and/or redox signaling.

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  1. Chance, 1965, Properties and kinetics of reduced pyridine nucleotide fluorescence of the isolated and in vivo rat heart, Biochem. Z., 341, 357

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Metadata

Authors
Cortassa, S., Aon, M. A., Winslow, R. L., & O’Rourke, B.
Affiliations
Johns Hopkins University (US)
ORCID
Venue
Biophysical Journal
Publisher
Elsevier BV
Published
2004-09
Volume
87
Issue
3
Pages
2060-2073
ISSN
0006-3495 (ISSN-L)
DOI
10.1529/biophysj.104.041749
PMC
PMC1304608
OpenAlex
W2058028795
Cited by
235
References
61
Citations by year
2026: 9 · 2025: 7 · 2024: 10 · 2023: 11 · 2022: 13 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 12 · 2017: 11 · 2016: 12 · 2015: 9 · 2014: 12 · 2013: 17 · 2012: 16
FWCI
3.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Biophysical Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (P50-HL52307, R01-HL-60133-01, R01HL105239, R01HL054598, R01HL060133, P50HL052307, R01HL54598)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › Nonlinear Dynamics and Pattern Formation
Keywords
reactive oxygen species, oxidative phosphorylation, cardiomyocytes, mitochondrial ROS production, glutathione redox state, calcium handling, redox signaling
MeSH terms
Animals, Calcium, Cytosol, Glutathione, Glutathione Peroxidase, Glutathione Reductase, Guinea Pigs, Hydrogen Peroxide, Image Processing, Computer-Assisted, Kinetics, Lasers, Membrane Potentials, Microscopy, Fluorescence, Mitochondria, Models, Biological, Models, Theoretical, Oligomycins, Oscillometry, Oxygen, Superoxide Dismutase, Reperfusion Injury, Reactive Oxygen Species, Photons, Myocytes, Cardiac

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