TY - JOUR
T1 - Diacylglycerols activate mitochondrial cationic channel(s) and release sequestered Ca2+
AU - Chinopoulos, Christos
AU - Starkov, Anatoly A.
AU - Grigoriev, Sergey
AU - Dejean, Laurent M.
AU - Kinnally, Kathleen W.
AU - Liu, Xibao
AU - Ambudkar, Indu S.
AU - Fiskum, Gary
N1 - Funding Information:
We thank Dr. Alicia J. Kowaltowski for help with the sweet potato mitochondrial isolation and Prof. Miklós Tóth and Dr. György Báthori for comments during the preparation of the manuscript. This work was supported by NIH grant GM57249 and NSF grant MCB-0235834 to K.W.K. and NIH grant NS34152 and USAMRMC grant DAMD 17-99-1-9483 to G.F.
PY - 2005/8
Y1 - 2005/8
N2 - 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.
AB - 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.
KW - Calcium
KW - Cation channel
KW - Diacylglycerol
KW - Mitochondria
KW - Mitoplast
KW - OAG
KW - Permeability transition pore
KW - Protein kinase C
KW - Transient receptor potential
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U2 - 10.1007/s10863-005-6634-0
DO - 10.1007/s10863-005-6634-0
M3 - Article
C2 - 16167179
AN - SCOPUS:26444435392
SN - 0145-479X
VL - 37
SP - 237
EP - 247
JO - Journal of Bioenergetics and Biomembranes
JF - Journal of Bioenergetics and Biomembranes
IS - 4
ER -