Sex-associated differences in mitochondrial function in human peripheral blood mononuclear cells (PBMCs) and brain
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BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia, and it affects more women than men. Mitochondrial dysfunction (MD) plays a key role in AD, and it is detectable at an early stage of the degenerative process in peripheral tissues, such as peripheral mononuclear blood cells (PBMCs). However, whether these changes are also reflected in cerebral energy metabolism and whether sex-specific differences in mitochondrial function occur are not clear. Therefore, we estimated the correlation between mitochondrial function in PBMCs and brain energy metabolites and examined sex-specific differences in healthy participants to elucidate these issues. METHODS: H-magnetic resonance spectroscopy (MRS). RESULTS: We detected sex-associated differences in mitochondrial function. Mitochondrial complexes I, I+II, and IV and uncoupled respiration and electron transport system (ETS) capacity in PBMCs isolated from blood samples of females were significantly (p < 0.05; p < 0.01) higher compared to males. ATP levels in the PBMCs of female participants were approximately 10% higher compared to males. Citrate synthase (CS) activity, a marker of mitochondrial content, was significantly (p < 0.05) higher in females compared to males. Sex-associated differences were also found for brain metabolites. The N-acetylaspartate (NAA) concentration was significantly higher in female participants compared to males in targeted regions. This difference was observed in white matter (WM) and an area with a high percentage (> 50%) of gray matter (GM) (p < 0.05; p < 0.01). The effect sizes indicated a strong influence of sex on these parameters. Sex-associated differences were found in PBMCs and brain, but the determined parameters were not significantly correlated. CONCLUSIONS: Our study revealed sex-associated differences in mitochondrial function in healthy participants. The underlying mechanisms must be elucidated in more detail, but our study suggests that mitochondrial function in PBMCs is a feasible surrogate marker to detect differences in mitochondrial function and energy metabolism in humans and it underscores the necessity of sex-specific approaches in therapies that target mitochondrial dysfunction.
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Important sex differences exist in mitochondrial function, substrate utilization, insulin sensitivity, immune responses, muscle morphology and body composition, iron metabolism, thermoregulation, hydration, appetite control, and energy availability and endocrine function.
“important sex differences exist in mitochondrial function [14–16], substrate utilization, and insulin sensitivity [17–24], immune responses [25–28], muscle morphology and body composition [29–32], iron metabolism [33–40], thermoregulation [41–44], hydration [45,46]{Sims, 2008 #55, [47–53], appetite control [54–59], and energy availability and endocrine function [60–65].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [14]
Female skeletal muscle has a greater abundance of the fatty acid transporter CD36 than male skeletal muscle, a sex difference that results in greater membrane translocation of CD36 during muscle contraction and helps explain heightened lipid metabolism in females compared to males during exercise.
“Miotto and colleagues [14] demonstrated that female skeletal muscle has a greater abundance of the fatty acid transporter CD36, a sex difference that results in a greater membrane translocation of the CD36 protein during muscle contraction that helps to explain the heightened rates of lipid metabolism, which occur in females when compared to males during exercise [160,161].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [14]
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- Authors
- Silaidos, C., Pilatus, U., Grewal, R., Matura, S., Lienerth, B., Pantel, J., & Eckert, G. P.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- Goethe University Frankfurt (DE)
- Corresponding author
- Eckert, G. P.
- Venue
- Biology of Sex Differences
- Published
- 2018-07-25
- Volume
- 9
- Issue
- 1
- Pages
- 34-34
- ISSN
- 2042-6410 (ISSN-L)
- PMC
- PMC6060503
- OpenAlex
- W2884114748
- Cited by
- 137
- References
- 69
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 27 · 2023: 21 · 2022: 18 · 2021: 17 · 2020: 16 · 2019: 4 · 2018: 1
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biology of Sex Differences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University writing server of the Justus Liebig University Giessen (Justus-Liebig-Universität Gießen) (submittedVersion, cc-by)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- sex differences, mitochondrial function, mitochondrial dysfunction, peripheral blood mononuclear cells, brain energy metabolism, Alzheimer's disease, mitochondrial protein complexes, uncoupled respiration, electron transport chain, ATP, citrate synthase, N-acetylaspartate, white matter, gray matter, magnetic resonance spectroscopy, surrogate markers
- MeSH terms
- Adenosine Triphosphate, Adult, Aspartic Acid, Brain, Citrate (si)-Synthase, Female, Humans, Leukocytes, Mononuclear, Male, Mitochondria, Sex Characteristics, Cell Respiration, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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