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Journal of Bioenergetics and Biomembranes

, Volume 37, Issue 4, pp 237–247 | Cite as

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
Article

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.

Keywords

Mitochondria calcium diacylglycerol mitoplast cation channel permeability transition pore protein kinase C transient receptor potential OAG 

Abbreviations:

1,2-DGs

1,2-Diacylglycerols

1,3-DGs

1,3-Diacylglycerols

2-MGs

2-Monoacylglycerols

1-MGs

1-Monoacylglycerols

ALM

Alamethicin

BKA

Bongkrekic acid

Cys A

Cyclosporin A

PTP

Permeability Transition Pore

OAG

1-oleoyl-acetyl-sn-glycerol

DOL

1,2-Dioleoylglycerol (18:1)

DDC

1,2-Didecanoylglycerol (10:0)

SAG

1-stearoyl-2-arachidonoyl-sn-glycerol

DOG

1,2-Dioctanoyl-sn-glycerol (8:0)

HDAG

1-O-Hexadecyl-2-arachidonoyl-sn-glycerol

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Christos Chinopoulos
    • 1
  • Anatoly A. Starkov
    • 2
  • Sergey Grigoriev
    • 3
  • Laurent M. Dejean
    • 3
  • Kathleen W. Kinnally
    • 3
  • Xibao Liu
    • 4
  • Indu S. Ambudkar
    • 4
  • Gary Fiskum
    • 1
    • 5
  1. 1.Department of AnesthesiologyUniversity of MarylandBaltimore
  2. 2.Department of NeurologyWeill Medical College, Cornell UniversityNew York
  3. 3.Division of Basic SciencesNew York University College of DentistryNew York
  4. 4.Secretory Physiology SectionGene Therapy and Therapeutics Branch, NIDCR, National Institutes of HealthBethesda
  5. 5.Department of AnesthesiologyUniversity of Maryland School of MedicineBaltimore

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