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

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 (US)
Pages (from-to)237-247
Number of pages11
JournalJournal of Bioenergetics and Biomembranes
Volume37
Issue number4
DOIs
StatePublished - Aug 2005

Fingerprint

Diglycerides
Mitochondria
Mitochondrial Membranes
Permeability
Bongkrekic Acid
Homeostasis
Mitochondrial Swelling
Monoglycerides
Protein C Inhibitor
Second Messenger Systems
Phorbol Esters
Protein Kinase Inhibitors
Constriction
Protein Kinase C
Cations
1,2-diacylglycerol
Brain

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Chinopoulos, C., Starkov, A. A., Grigoriev, S., Dejean, L. M., Kinnally, K. W., Liu, X., ... 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

Diacylglycerols activate mitochondrial cationic channel(s) and release sequestered Ca2+. / Chinopoulos, Christos; Starkov, Anatoly A.; Grigoriev, Sergey; Dejean, Laurent M.; Kinnally, Kathleen W.; Liu, Xibao; Ambudkar, Indu S.; Fiskum, Gary.

In: Journal of Bioenergetics and Biomembranes, Vol. 37, No. 4, 08.2005, p. 237-247.

Research output: Contribution to journalArticle

Chinopoulos, C, Starkov, AA, Grigoriev, S, Dejean, LM, Kinnally, KW, Liu, X, Ambudkar, IS & Fiskum, G 2005, 'Diacylglycerols activate mitochondrial cationic channel(s) and release sequestered Ca2+', Journal of Bioenergetics and Biomembranes, vol. 37, no. 4, pp. 237-247. https://doi.org/10.1007/s10863-005-6634-0
Chinopoulos, Christos ; Starkov, Anatoly A. ; Grigoriev, Sergey ; Dejean, Laurent M. ; Kinnally, Kathleen W. ; Liu, Xibao ; Ambudkar, Indu S. ; Fiskum, Gary. / Diacylglycerols activate mitochondrial cationic channel(s) and release sequestered Ca2+. In: Journal of Bioenergetics and Biomembranes. 2005 ; Vol. 37, No. 4. pp. 237-247.
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