Lithium isotopes differentially modify mitochondrial amorphous calcium phosphate cluster size distribution and calcium capacity
Open accessAbstract
Lithium is commonly prescribed as a mood stabilizer in a variety of mental health conditions, yet its molecular mode of action is incompletely understood. Many cellular events associated with lithium appear tied to mitochondrial function. Further, recent evidence suggests that lithium bioactivities are isotope specific. Here we focus on lithium effects related to mitochondrial calcium handling. Lithium protected against calcium-induced permeability transition and decreased the calcium capacity of liver mitochondria at a clinically relevant concentration. In contrast, brain mitochondrial calcium capacity was increased by lithium. Surprisingly, 7 Li acted more potently than 6 Li on calcium capacity, yet 6 Li was more effective at delaying permeability transition. The size distribution of amorphous calcium phosphate colloids formed in vitro was differentially affected by lithium isotopes, providing a mechanistic basis for the observed isotope specific effects on mitochondrial calcium handling. This work highlights a need to better understand how mitochondrial calcium stores are structurally regulated and provides key considerations for future formulations of lithium-based therapeutics.
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“Furthermore, experiments on Posner clusters have been conducted to provide insights into their properties, but their coherence has not yet been studied experimentally [92,93,94,95,96].”
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- Authors
- Deline, M. L., Straub, J., Patel, M., Subba, P., Grashei, M., van Heijster, F. H. A., Pirkwieser, P., Somoza, V., Livingstone, J. D., Beazely, M., Kendall, B., Gingras, M. J. P., Leonenko, Z., Höschen, C., Harrington, G., Kuellmer, K., Bian, W., Schilling, F., Fisher, M. P. A., Helgeson, M. E., & Fromme, T.
- Affiliations
- Technical University of Munich (DE)
- University of California, Santa Barbara (US)
- TUM Klinikum (DE)
- Leibniz-Institute for Food Systems Biology at the Technical University of Munich (DE)
- University of Waterloo (CA)
- Canadian Institute for Advanced Research (CA)
- Else Kröner Fresenius Zentrum für Ernährungsmedizin (DE)
- Corresponding author
- Fromme, Tobias
- ORCID
- Venue
- Frontiers in Physiology
- Publisher
- Frontiers Media SA
- Published
- 2023-09-15
- Volume
- 14
- Pages
- 1200119-1200119
- ISSN
- 1664-042X (ISSN-L)
- PMC
- PMC10540846
- OpenAlex
- W4386836810
- Cited by
- 8
- References
- 59
- Citations by year
- 2025: 5 · 2024: 3
- FWCI
- 0.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Physiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- Ionis Pharmaceuticals
- European Commission (HORIZON2020, 820374)
- Deutsche Forschungsgemeinschaft (391523415, SFB824, 450149205)
- Canada Research Chairs
- Else Kröner-Fresenius-Stiftung
- University of Waterloo
- Technische Universität München
- Bayerische Akademie der Wissenschaften
- 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 › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- lithium isotopes, lithium-7, lithium-6, mitochondrial calcium handling, amorphous calcium phosphate, permeability transition, liver mitochondria, brain mitochondria, mood stabilizers
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