Gender modulation of Ca2+ uptake in cardiac mitochondria
Abstract
Background Mitochondrial calcium overload is an important factor in defining ischemia/reperfusion injury. Since pre-menopausal women are relatively protected from ischemia and heart disease, we tested the hypothesis that gender differences alter Ca(2+) handling in rat cardiac mitochondria.Methods Using cardiac mitochondria isolated from male, female, and ovariectomized Sprague-Dawley rats, we measured mitochondrial calcium transport, redox state, and membrane potential (Deltapsi(m)) during exposure to a calcium bolus. Redox state was modulated using either succinate (S) or succinate and pyruvate (SP) as substrates.Results Net Ca(2+) uptake rates were significantly lower in female than male mitochondria using SP, substrate conditions that resulted in a lower redox state (NADH/NAD(+)). Inhibition of the mitochondrial transition pore (MTP) using cyclosporin A showed significantly lower net Ca(2+) uptake in both substrate solutions when mitochondria from female and ovariectomized animals were compared to males, a finding consistent with gender modulation of the mitochondrial uniporter. Blockade of the Ca(2+) uniporter by ruthenium red abolished gender or substrate solution differences in calcium release. While there were no significant differences in resting Deltapsi(m), or Deltapsi(m) following Ca(2+) addition, 80% of female samples recovered from Ca(2+)-induced depolarization compared to 57% and 43% of male and ovariectomized animals, respectively.Conclusions Mitochondria from female hearts have lower Ca(2+) uptake rates under physiologic substrate solutions (succinate/pyruvate) and are able to appropriately maintain DeltaYm under conditions of high [Ca(2+)]. These differences are consistent with gender modulation of the Ca(2+) uniporter and may be a mechanism by which female myocardium suffers less injury with ischemia/reperfusion.
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Female brain and heart mitochondria have lower Ca2+ uptake than males.
“Conversely, the female brain and heart mitochondria have lower Ca2+ uptake than males (105, 106).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [106]
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Dhalla, N. S., Vijayan Elimban, A., Hryshko, L. V., & Freed, D. H. (2013) · Springer eBooks · doi:10.1007/978-1-4614-5930-9_16
Sex differences in neutrophil extracellular trap formation
Yuan, X. Z. (2018) · TSpace (University of Toronto)
(Sex differences in cardiac tolerance to ischemia-reperfusion injury - the role of mitochondria)
Ošťádal, B., Drahota, Z., Ošťádal, P., & Neckář, J. (2021) · Cor et Vasa · doi:10.33678/cor.2021.023
Ji, X., Li, P., & Zhao, Y. S. (2024) · IEEE International Conference on Bioinformatics and Biomedicine (BIBM) · doi:10.1109/bibm62325.2024.10822605
- Authors
- ARIELI, Y.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- ARIELI, Y
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 37
- Issue
- 2
- Pages
- 507-513
- ISSN
- 0022-2828 (ISSN-L)
- OpenAlex
- W2063830130
- Cited by
- 72
- References
- 30
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 7 · 2019: 8 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 5 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- mitochondrial calcium uptake, heart mitochondria, sex differences, ovariectomy, mitochondrial calcium uniporter, cyclosporine, ruthenium red, mitochondrial membrane potential, mitochondrial redox state, succinic acid, pyruvate, ischemia-reperfusion injury
- MeSH terms
- Animals, Biological Transport, Calcium, Female, Male, Mitochondria, Myocardium, NAD, Sex Factors, Cyclosporine, Rats
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