Sex-specific differences in mitochondria biogenesis, morphology, respiratory function, and ros homeostasis in young mouse heart and brain
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Abstract Sex‐specific differences in mitochondrial function and free radical homeostasis are reported in the context of aging but not well‐established in pathogeneses occurring early in life. Here, we examine if sex disparity in mitochondria function, morphology, and redox status starts early and hence can be implicated in sexual dimorphism in cardiac as well as neurological disorders prevalent at young age. Although mitochondrial activity in the heart did not significantly vary between sexes, female brain exhibited enhanced respiration and higher reserve capacity. This was associated with lower H 2 O 2 production in female cardiac and brain tissues. Using transmission electron microscopy, we found that the number of female cardiac mitochondria is moderately greater (117 ± 3%, P = 0.049, N = 4) than male's, which increased significantly for cortical mitochondria (134 ± 4%, P = 0.001, N = 4). However, male's cardiac mitochondria exhibited fragmented, circular, and smaller mitochondria relative to female's mitochondria, while no morphologic sex‐dependent differences were observed in cortical mitochondria. No sex differences were detected in Nox2 and Nox4 proteins or O 2 ‐consuming/H 2 O 2 ‐producing activities in brain homogenate or synaptosomes. However, a strong trend of increased EPR ‐detected NOX superoxide in male synaptosomes hinted at higher superoxide dismutase activity in female brains, which was confirmed by two independent protocols. We also provide direct evidence that respiring mitochondria generally produce an order‐of‐magnitude lower reactive oxygen species ( ROS ) proportions than currently estimated. Our results indicate that sex differences in mitochondrial biogenesis, bioenergetics, and morphology may start at young age and that sex‐dependent SOD capacity may be responsible for differences in ROS homeostasis in heart and brain.
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Female mitochondria in the heart, liver, and brain have a higher antioxidant capacity and produce less ROS than males.
“For instance, female mitochondria in the heart, liver, and brain have a higher antioxidant capacity and produce less ROS than males (101, 102).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [101]
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- Authors
- Khalifa, A. R. M., Abdel‐Rahman, E. A., Mahmoud, A. M., Ali, M. H., Noureldin, M., Saber, S. H., Mohsen, M., & Ali, S. S.
- Affiliations
- Zewail City of Science and Technology (EG)
- Center for Aging and Associated Diseases Helmy Institute of Medical Sciences Zewail City of Science and Technology Giza Egypt
- Corresponding author
- Ali, Sameh S.
- Venue
- Physiological Reports
- Publisher
- Wiley
- Published
- 2017-03
- Volume
- 5
- Issue
- 6
- ISSN
- 2051-817X (ISSN-L)
- PMC
- PMC5371549
- OpenAlex
- W2599149063
- Cited by
- 154
- References
- 51
- Citations by year
- 2026: 15 · 2025: 19 · 2024: 22 · 2023: 14 · 2022: 16 · 2021: 17 · 2020: 18 · 2019: 20 · 2018: 8 · 2017: 5
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Physiological Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Zewail City of Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- sex differences, mitochondrial biogenesis, mitochondrial morphology, mitochondrial respiration, reactive oxygen species homeostasis, superoxide dismutase, heart, brain, cortical mitochondria, hydrogen peroxide, NADPH oxidase, synaptosomes, mitochondrial fragmentation, young adult mice, cardiac bioenergetics
- MeSH terms
- Aging, Animals, Organelle Biogenesis, Brain, Female, Homeostasis, Male, Mitochondria, Mitochondria, Heart, Myocardium, Oxidation-Reduction, Oxygen Consumption, Sex Characteristics, Superoxides, Reactive Oxygen Species, NADPH Oxidases, Mice
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