ArticleThe Journal of biological chemistry2011
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.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 103 citations in OpenAlex.
- How does mitochondrial Ca2+ change during ischemia and reperfusion? Implications for activation of the permeability transition pore.The Journal of general physiology · 2025Review
- Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases.npj metabolic health and disease · 2025Review
- Calcium signaling in mitochondrial intermembrane space.Biochemical Society transactions · 2024Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Mitochondrial calcium uniporter channel gatekeeping in cardiovascular disease.Nature cardiovascular research · 2024Review
- Improved mitochondrial function in the hearts of sarcolipin-deficient dystrophin and utrophin double-knockout mice.JCI insight · 2024Article
- Bi-allelic LETM1 variants perturb mitochondrial ion homeostasis leading to a clinical spectrum with predominant nervous system involvement.American journal of human genetics · 2022Article
- MICU1 controls spatial membrane potential gradients and guides CaCommunications biology · 2022Article
- Mitochondrial calcium exchange in physiology and disease.Physiological reviews · 2022Review
- Mitochondrial CaInternational journal of molecular sciences · 2022Review
- The interplay between mitochondria and store-operated CaJournal of cellular and molecular medicine · 2021Review
- A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance.Science advances · 2021Article
- Sarcoplasmic reticulum-mitochondria communication; implications for cardiac arrhythmia.Journal of molecular and cellular cardiology · 2021Review
- LETM1: A Single Entity With Diverse Impact on Mitochondrial Metabolism and Cellular Signaling.Frontiers in physiology · 2021Review
- Xanthohumol ameliorates Diet-Induced Liver Dysfunction via Farnesoid X Receptor-Dependent and Independent Signaling.Frontiers in pharmacology · 2021Article
- Dynamic Control of Mitochondrial CaFrontiers in cell and developmental biology · 2021Article
- Regulation of Cell Death by Mitochondrial Transport Systems of Calcium and Bcl-2 Proteins.Membranes · 2020Review
- Tracking intra- and inter-organelle signaling of mitochondria.The FEBS journal · 2019Review
- Article
- LETM1 is required for mitochondrial homeostasis and cellular viability (Review).Molecular medicine reports · 2019Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.