TY - JOUR
T1 - Lithium isotopes differentially modify mitochondrial amorphous calcium phosphate cluster size distribution and calcium capacity
AU - Deline, Marshall L.
AU - Straub, Joshua
AU - Patel, Manisha
AU - Subba, Pratigya
AU - Grashei, Martin
AU - van Heijster, Frits H.A.
AU - Pirkwieser, Philip
AU - Somoza, Veronika
AU - Livingstone, James D.
AU - Beazely, Michael
AU - Kendall, Brian
AU - Gingras, Michel J.P.
AU - Leonenko, Zoya
AU - Höschen, Carmen
AU - Harrington, Gertraud
AU - Kuellmer, Katharina
AU - Bian, Wangqing
AU - Schilling, Franz
AU - Fisher, Matthew P.A.
AU - Helgeson, Matthew E.
AU - Fromme, Tobias
N1 - Publisher Copyright:
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.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - amorphous calcium phosphate
KW - calcium
KW - isotope distribution
KW - lithium
KW - lithium bioactivity
KW - mitochondria
KW - mitochondrial calcium
UR - http://www.scopus.com/inward/record.url?scp=85173124268&partnerID=8YFLogxK
U2 - 10.3389/fphys.2023.1200119
DO - 10.3389/fphys.2023.1200119
M3 - Article
AN - SCOPUS:85173124268
SN - 1664-042X
VL - 14
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - 1200119
ER -
