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SHR Neuro Cancer Cardio Lipid Metab Microb

Waldeck-Weiermair, M; Jean-Quartier, C; Rost, R; Khan, MJ; Vishnu, N; Bondarenko, AI; Imamura, H; Malli, R; Graier, WF.
Leucine Zipper EF Hand-containing Transmembrane Protein 1 (Letm1) and Uncoupling Proteins 2 and 3 (UCP2/3) Contribute to Two Distinct Mitochondrial Ca2+ Uptake Pathways.
J Biol Chem. 2011; 286(32):28444-28455 Doi: 10.1074/jbc.M111.244517 [OPEN ACCESS]
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Leading authors Med Uni Graz: Graier Wolfgang; Waldeck-Weiermair Markus
Co-authors Med Uni Graz: Bondarenko Oleksandr; Jean-Quartier Claire; Khan Muhammad Jadoon; Malli Roland; Rost René; Vishnu Neelanjan
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Abstract:: Cytosolic Ca(2+) signals are transferred into mitochondria over a huge concentration range. In our recent work we described uncoupling proteins 2 and 3 (UCP2/3) to be fundamental for mitochondrial uptake of high Ca(2+) domains in mitochondria-ER junctions. On the other hand, the leucine zipper EF hand-containing transmembrane protein 1 (Letm1) was identified as a mitochondrial Ca(2+)/H(+) antiporter that achieved mitochondrial Ca(2+) sequestration at small Ca(2+) increases. Thus, the contributions of Letm1 and UCP2/3 to mitochondrial Ca(2+) uptake were compared in endothelial cells. Knock-down of Letm1 did not affect the UCP2/3-dependent mitochondrial uptake of intracellularly released Ca(2+) but strongly diminished the transfer of entering Ca(2+) into mitochondria, subsequently, resulting in a reduction of store-operated Ca(2+) entry (SOCE). Knock-down of Letm1 and UCP2/3 did neither impact on cellular ATP levels nor the membrane potential. The enhanced mitochondrial Ca(2+) signals in cells overexpressing UCP2/3 rescued SOCE upon Letm1 knock-down. In digitonin-permeabilized cells, Letm1 exclusively contributed to mitochondrial Ca(2+) uptake at low Ca(2+) conditions. Neither the Letm1- nor the UCP2/3-dependent mitochondrial Ca(2+) uptake was affected by a knock-down of mRNA levels of mitochondrial calcium uptake 1 (MICU1), a protein that triggers mitochondrial Ca(2+) uptake in HeLa cells. Our data indicate that Letm1 and UCP2/3 independently contribute to two distinct, mitochondrial Ca(2+) uptake pathways in intact endothelial cells.
Find related publications in this database (using NLM MeSH Indexing): Calcium - metabolism; Calcium Signaling - physiology; Calcium-Binding Proteins - genetics; Cation Transport Proteins - genetics; Endothelial Cells - cytology; Gene Knockdown Techniques -; HeLa Cells -; Humans -; Ion Channels - genetics; Membrane Proteins - genetics; Mitochondria - genetics; Mitochondrial Membrane Transport Proteins - genetics; Mitochondrial Proteins - genetics; RNA, Messenger - genetics