Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

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 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Bondarenko Oleksandr
Graier Wolfgang
Jean-Quartier Claire
Khan Muhammad Jadoon
Malli Roland
Rost René
Vishnu Neelanjan
Waldeck-Weiermair Markus
Altmetrics:

Dimensions Citations:

Plum Analytics:
Number of Figures: 9
| | | | | | | | |
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

© Meduni Graz Impressum