Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 288, Issue 21, Pages 15367-15379Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.462259
Keywords
-
Categories
Funding
- Austrian Science Funds (FWF) [P20181-B05, P21857-B18, P22553-B18]
- FWF within the PhD program Neuroscience at the Medical University of Graz
- FWF within the PhD program MolMed of the Medical University of Graz
- Austrian Science Fund (FWF) [P 22553, P 21857] Funding Source: researchfish
- Austrian Science Fund (FWF) [P20181, P21857, P22553] Funding Source: Austrian Science Fund (FWF)
Ask authors/readers for more resources
The transfer of Ca2+ across the inner mitochondrial membrane is an important physiological process linked to the regulation of metabolism, signal transduction, and cell death. While the definite molecular composition of mitochondrial Ca2+ uptake sites remains unknown, several proteins of the inner mitochondrial membrane, that are likely to accomplish mitochondrial Ca2+ fluxes, have been described: the novel uncoupling proteins 2 and 3, the leucine zipper-EF-hand containing transmembrane protein 1 and the mitochondrial calcium uniporter. It is unclear whether these proteins contribute to one unique mitochondrial Ca2+ uptake pathway or establish distinct routes for mitochondrial Ca2+ sequestration. In this study, we show that a modulation of Ca2+ release from the endoplasmic reticulum by inhibition of the sarco/endoplasmatic reticulum ATPase modifies cytosolic Ca2+ signals and consequently switches mitochondrial Ca2+ uptake from an uncoupling protein 3- and mitochondrial calcium uniporter-dependent, but leucine zipper-EF-hand containing transmembrane protein 1-independent to a leucine zipper-EF-hand containing transmembrane protein 1- and mitochondrial calcium uniporter-mediated, but uncoupling protein 3-independent pathway. Thus, the activity of sarco/endoplasmatic reticulum ATPase is significant for the mode of mitochondrial Ca2+ sequestration and determines which mitochondrial proteins might actually accomplish the transfer of Ca2+ across the inner mitochondrial membrane. Moreover, our findings herein support the existence of distinct mitochondrial Ca2+ uptake routes that might be essential to ensure an efficient ion transfer into mitochondria despite heterogeneous cytosolic Ca2+ rises.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available