Diacylglycerols activate mitochondrial cationic channel(s) and release sequestered Ca2+ Academic Article uri icon

Overview

MeSH Major

  • Calcium
  • Diglycerides
  • Ion Channels
  • Mitochondria

abstract

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

publication date

  • August 2005

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2600847

Digital Object Identifier (DOI)

  • 10.1007/s10863-005-6634-0

PubMed ID

  • 16167179

Additional Document Info

start page

  • 237

end page

  • 47

volume

  • 37

number

  • 4