Lithium isotopes differentially modify mitochondrial amorphous calcium phosphate cluster size distribution and calcium capacity

Frontiers in Physiology

Physiology

Katharina Kuellmer¹  Pratigya Subba¹  Wangqing Bian¹  Marshall L. Deline¹  Tobias Fromme²  Gertraud Harrington³  Carmen Höschen³  Matthew E. Helgeson⁴  Brian Kendall⁵  Franz Schilling⁶  Frits H. A. van Heijster⁶  Martin Grashei⁶  Michel J. P. Gingras⁷  Zoya Leonenko⁸  Manisha Patel⁹  Joshua Straub⁹  Matthew P. A. Fisher⁹  Philip Pirkwieser^1,10  Veronika Somoza^1,11  James D. Livingstone^1,12  Michael Beazely^1,12 

[1] Chair of Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany;Chair of Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany;EKFZ—Else Kröner-Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany;Chair of Soil Science, TUM School of Life Sciences, Technical University of Munich, Munich, Germany;Department of Chemical Engineering, University of California, Santa Barbara, CA, United States;Department of Earth and Environmental Sciences, University of Waterloo, Waterloo, ON, Canada;Department of Nuclear Medicine, TUM School of Medicine, Technical University of Munich, Munich, Germany;Department of Physics and Astronomy, University of Waterloo, Waterloo, ON, Canada;CIFAR, MaRS Centre, Toronto, ON, Canada;Department of Physics and Astronomy, University of Waterloo, Waterloo, ON, Canada;Department of Biology, University of Waterloo, Waterloo, ON, Canada;Department of Physics, University of California, Santa Barbara, CA, United States;Leibniz Institute for Food Systems Biology at the Technical University of Munich, Freising, Germany;Leibniz Institute for Food Systems Biology at the Technical University of Munich, Freising, Germany;Chair of Nutritional Systems Biology, TUM School of Life Sciences, Technical University of Munich, Munich, Germany;School of Pharmacy, University of Waterloo, Waterloo, ON, Canada;

关键词: mitochondria;    calcium;    mitochondrial calcium;    lithium;    lithium bioactivity;    amorphous calcium phosphate;    isotope distribution;   

DOI  :  10.3389/fphys.2023.1200119

 received in 2023-04-04, accepted in 2023-08-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

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, 7Li acted more potently than 6Li on calcium capacity, yet 6Li 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.

【 授权许可】

Unknown   
Copyright © 2023 Deline, Straub, Patel, Subba, Grashei, van Heijster, Pirkwieser, Somoza, Livingstone, Beazely, Kendall, Gingras, Leonenko, Höschen, Harrington, Kuellmer, Bian, Schilling, Fisher, Helgeson and Fromme.