Diacylglycerols activate mitochondrial cationic channel(s) and release sequestered Ca2+

Christos Chinopoulos, Anatoly A. Starkov, Sergey Grigoriev, Laurent M. Dejean, Kathleen W. Kinnally, Xibao Liu, Indu S. Ambudkar, Gary Fiskum

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Mitochondria contribute to cytosolic Ca2+ homeostasis through several uptake and release pathways. Here we report that 1,2-sn-diacylglycerols (DAGs) induce Ca2+ release from Ca2+-loaded mammalian mitochondria. Release is not mediated by the uniporter or the Na +/Ca2+ exchanger, nor is it attributed to putative catabolites. DAGs-induced Ca2+ efflux is biphasic. Initial release is rapid and transient, insensitive to permeability transition inhibitors, and not accompanied by mitochondrial swelling. Following initial rapid release of Ca2+ and relatively slow reuptake, a secondary progressive release of Ca2+ occurs, associated with swelling, and mitigated by permeability transition inhibitors. The initial peak of DAGs-induced Ca2+ efflux is abolished by La3+ (1 mM) and potentiated by protein kinase C inhibitors. Phorbol esters, 1,3-diacylglycerols and 1-monoacylglycerols do not induce mitochondrial Ca2+ efflux. Ca2+-loaded mitoplasts devoid of outer mitochondrial membrane also exhibit DAGs-induced Ca2+ release, indicating that this mechanism resides at the inner mitochondrial membrane. Patch clamping brain mitoplasts reveal DAGs-induced slightly cation-selective channel activity that is insensitive to bongkrekic acid and abolished by La3+. The presence of a second messenger-sensitive Ca2+ release mechanism in mitochondria could have an important impact on intracellular Ca2+ homeostasis.

Original languageEnglish
Pages (from-to)237-247
Number of pages11
JournalJournal of Bioenergetics and Biomembranes
Volume37
Issue number4
DOIs
Publication statusPublished - Aug 2005

Keywords

  • Calcium
  • Cation channel
  • Diacylglycerol
  • Mitochondria
  • Mitoplast
  • OAG
  • Permeability transition pore
  • Protein kinase C
  • Transient receptor potential

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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    Chinopoulos, C., Starkov, A. A., Grigoriev, S., Dejean, L. M., Kinnally, K. W., Liu, X., Ambudkar, I. S., & Fiskum, G. (2005). Diacylglycerols activate mitochondrial cationic channel(s) and release sequestered Ca2+. Journal of Bioenergetics and Biomembranes, 37(4), 237-247. https://doi.org/10.1007/s10863-005-6634-0