ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
LETM1-dependent mitochondrial Ca2+ flux modulates cellular bioenergetics and proliferation.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 70 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
70 citing papers in PubMed, 105 citations in OpenAlex.
- Mitochondria-ER contact sites (MERCS) in the cell cycle: molecular architecture and functional remodeling across cellular states.BMC biology · 2026Review
- Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases.npj metabolic health and disease · 2025Review
- The Role of Autophagy in Excitotoxicity, Synaptic Mitochondrial Stress and Neurodegeneration.Autophagy reports · 2025Article
- Calcium signaling in mitochondrial intermembrane space.Biochemical Society transactions · 2024Review
- Mitochondrial Calcium Regulation of Cardiac Metabolism in Health and Disease.Physiology (Bethesda, Md.) · 2024Review
- Dissecting structure and function of the monovalent cation/HJournal of bacteriology · 2024Article
- Excitotoxicity, Oxytosis/Ferroptosis, and Neurodegeneration: Emerging Insights into Mitochondrial Mechanisms.Aging and disease · 2024Review
- Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma.Genes & diseases · 2024Article
- MCU-independent CaScientific reports · 2024Article
- Beyond the TCA cycle: new insights into mitochondrial calcium regulation of oxidative phosphorylation.Biochemical Society transactions · 2023Review
- Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice.Nature communications · 2023Article
- TMBIM5 is the CaEMBO reports · 2022Article
- Bi-allelic LETM1 variants perturb mitochondrial ion homeostasis leading to a clinical spectrum with predominant nervous system involvement.American journal of human genetics · 2022Article
- Mitochondrial calcium exchange in physiology and disease.Physiological reviews · 2022Review
- Mitochondria modulate ameloblast CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration.Translational neurodegeneration · 2022Review
- Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins inInternational journal of molecular sciences · 2021Article
- Metabolic Remodeling and Implicated Calcium and Signal Transduction Pathways in the Pathogenesis of Heart Failure.International journal of molecular sciences · 2021Review
- Trypanosoma cruzi Letm1 is involved in mitochondrial CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- The leucine zipper EF-hand containing transmembrane protein-1 EF-hand is a tripartite calcium, temperature, and pH sensor.Protein science : a publication of the Protein Society · 2021Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedERRATUM.2015
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Dysregulation of mitochondrial Ca(2+)-dependent bioenergetics has been implicated in various pathophysiological settings, including neurodegeneration and myocardial infarction. Although mitochondrial Ca(2+) transport has been characterized, and several molecules, including LETM1, have been identified, the functional role of LETM1-mediated Ca(2+) transport remains unresolved. This study examines LETM1-mediated mitochondrial Ca(2+) transport and bioenergetics in multiple cell types, including fibroblasts derived from patients with Wolf-Hirschhorn syndrome (WHS). The results show that both mitochondrial Ca(2+) influx and efflux rates are impaired in LETM1 knockdown, and similar phenotypes were observed in ΔEF hand, (D676A D688K)LETM1 mutant-overexpressed cells, and in cells derived from patients with WHS. Although LETM1 levels were lower in WHS-derived fibroblasts, the mitochondrial Ca(2+) uniporter components MCU, MCUR1, and MICU1 remain unaltered. In addition, the MCU mitoplast patch-clamp current (IMCU) was largely unaffected in LETM1-knockdown cells. Silencing of LETM1 also impaired basal mitochondrial oxygen consumption, possibly via complex IV inactivation and ATP production. Remarkably, LETM1 knockdown also resulted in increased reactive oxygen species production. Further, LETM1 silencing promoted AMPK activation, autophagy, and cell cycle arrest. Reconstitution of LETM1 or antioxidant overexpression rescued mitochondrial Ca(2+) transport and bioenergetics. These findings reveal the role of LETM1-dependent mitochondrial Ca(2+) flux in shaping cellular bioenergetics.
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Registered trials
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.