scholarly journals Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) forms a Ca2+/H+ antiporter

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Juan Shao ◽  
Zhenglin Fu ◽  
Yanli Ji ◽  
Xiangchen Guan ◽  
Shang Guo ◽  
...  
Keyword(s):  
Leucine Zipper ◽  
Transmembrane Protein ◽  
Ef Hand

scholarly journals Functional reconstitution of the mitochondrial Ca2+/H+ antiporter Letm1

2013 ◽  
Vol 143 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Ming-Feng Tsai ◽  
Dawei Jiang ◽  
Linlin Zhao ◽  
David Clapham ◽  
Christopher Miller
Keyword(s):  
Transport Mechanism ◽  
Turnover Rate ◽  
Leucine Zipper ◽  
Transmembrane Protein ◽  
Ruthenium Red ◽  
Mitochondrial Calcium Uniporter ◽  
Mitochondrial Inner Membrane ◽  
Calcium Uniporter ◽  
Ef Hand ◽  
Inner Membrane Protein

The leucine zipper, EF hand–containing transmembrane protein 1 (Letm1) gene encodes a mitochondrial inner membrane protein, whose depletion severely perturbs mitochondrial Ca2+ and K+ homeostasis. Here we expressed, purified, and reconstituted human Letm1 protein in liposomes. Using Ca2+ fluorophore and 45Ca2+-based assays, we demonstrate directly that Letm1 is a Ca2+ transporter, with apparent affinities of cations in the sequence of Ca2+ ≈ Mn2+ > Gd3+ ≈ La3+ > Sr2+ >> Ba2+, Mg2+, K+, Na+. Kinetic analysis yields a Letm1 turnover rate of 2 Ca2+/s and a Km of ∼25 µM. Further experiments show that Letm1 mediates electroneutral 1 Ca2+/2 H+ antiport. Letm1 is insensitive to ruthenium red, an inhibitor of the mitochondrial calcium uniporter, and CGP-37157, an inhibitor of the mitochondrial Na+/Ca2+ exchanger. Functional properties of Letm1 described here are remarkably similar to those of the H+-dependent Ca2+ transport mechanism identified in intact mitochondria.

Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand-containing transmembrane protein-1 plays a role in apoptosis

2009 ◽  
Vol 21 (5) ◽  
pp. 767-777 ◽  
Author(s):  
Longzhen Piao ◽  
Yuwen Li ◽  
Soung Jung Kim ◽  
Kyung-Cheol Sohn ◽  
Keum-Jin Yang ◽  
...  
Keyword(s):  
Leucine Zipper ◽  
Transmembrane Protein ◽  
Mitochondrial Fusion ◽  
Ef Hand

scholarly journals Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and Disease

2019 ◽  
Vol 20 (2) ◽  
pp. 286 ◽  
Author(s):  
Qi-Tong Lin ◽  
Peter Stathopulos
Keyword(s):  
Leucine Zipper ◽  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Cell Physiology ◽  
Inner Mitochondrial Membrane ◽  
Atp Production ◽  
Transporter Protein ◽  
Mitochondrial Functions ◽  
Ef Hand ◽  
Mechanistic Basis

Mitochondrial calcium (Ca2+) uptake shapes cytosolic Ca2+ signals involved in countless cellular processes and more directly regulates numerous mitochondrial functions including ATP production, autophagy and apoptosis. Given the intimate link to both life and death processes, it is imperative that mitochondria tightly regulate intramitochondrial Ca2+ levels with a high degree of precision. Among the Ca2+ handling tools of mitochondria, the leucine zipper EF-hand containing transmembrane protein-1 (LETM1) is a transporter protein localized to the inner mitochondrial membrane shown to constitute a Ca2+/H+ exchanger activity. The significance of LETM1 to mitochondrial Ca2+ regulation is evident from Wolf-Hirschhorn syndrome patients that harbor a haplodeficiency in LETM1 expression, leading to dysfunctional mitochondrial Ca2+ handling and from numerous types of cancer cells that show an upregulation of LETM1 expression. Despite the significance of LETM1 to cell physiology and pathophysiology, the molecular mechanisms of LETM1 function remain poorly defined. In this review, we aim to provide an overview of the current understanding of LETM1 structure and function and pinpoint the knowledge gaps that need to be filled in order to unravel the underlying mechanistic basis for LETM1 function.

scholarly journals Priority Strategy of Intracellular Ca2+ Homeostasis in Skeletal Muscle Fibers during the Multiple Stresses of Hibernation

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 42 ◽  
Author(s):  
Jie Zhang ◽  
Xiaoyu Li ◽  
Fazeela Ismail ◽  
Shenhui Xu ◽  
Zhe Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Leucine Zipper ◽  
Binding Capacity ◽  
Transmembrane Protein ◽  
Muscle Fibers ◽  
Vital Role ◽  
Ground Squirrels ◽  
Calcium Uniporter ◽  
Skeletal Muscle Fibers ◽  
Ef Hand

Intracellular calcium (Ca2+) homeostasis plays a vital role in the preservation of skeletal muscle. In view of the well-maintained skeletal muscle found in Daurian ground squirrels (Spermophilus dauricus) during hibernation, we hypothesized that hibernators possess unique strategies of intracellular Ca2+ homeostasis. Here, cytoplasmic, sarcoplasmic reticulum (SR), and mitochondrial Ca2+ levels, as well as the potential Ca2+ regulatory mechanisms, were investigated in skeletal muscle fibers of Daurian ground squirrels at different stages of hibernation. The results showed that cytoplasmic Ca2+ levels increased in the skeletal muscle fibers during late torpor (LT) and inter-bout arousal (IBA), and partially recovered when the animals re-entered torpor (early torpor, ET). Furthermore, compared with levels in the summer active or pre-hibernation state, the activity and protein expression levels of six major Ca2+ channels/proteins were up-regulated during hibernation, including the store-operated Ca2+ entry (SOCE), ryanodine receptor 1 (RyR1), leucine zipper-EF-hand containing transmembrane protein 1 (LETM1), SR Ca2+ ATPase 1 (SERCA1), mitochondrial calcium uniporter complex (MCU complex), and calmodulin (CALM). Among these, the increased extracellular Ca2+ influx mediated by SOCE, SR Ca2+ release mediated by RyR1, and mitochondrial Ca2+ extrusion mediated by LETM1 may be triggers for the periodic elevation in cytoplasmic Ca2+ levels observed during hibernation. Furthermore, the increased SR Ca2+ uptake through SERCA1, mitochondrial Ca2+ uptake induced by MCU, and elevated free Ca2+ binding capacity mediated by CALM may be vital strategies in hibernating ground squirrels to attenuate cytoplasmic Ca2+ levels and restore Ca2+ homeostasis during hibernation. Compared with that in LT or IBA, the decreased extracellular Ca2+ influx mediated by SOCE and elevated mitochondrial Ca2+ uptake induced by MCU may be important mechanisms for the partial cytoplasmic Ca2+ recovery in ET. Overall, under extreme conditions, hibernating ground squirrels still possess the ability to maintain intracellular Ca2+ homeostasis.

scholarly journals High Expression of Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Predicts Poor Prognosis in Head and Neck Squamous Cell Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Liyan Chen ◽  
Yang Yang ◽  
Shuangping Liu ◽  
Longzhen Piao ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Leucine Zipper ◽  
Transmembrane Protein ◽  
Neck Squamous Cell Carcinoma ◽  
High Expression ◽  
Advanced Stage ◽  
Ef Hand

Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial inner membrane protein and plays an important role in mitochondrial ATP production and biogenesis. High expression levels of LETM1 have been correlated with numerous human malignancies. This study explored the clinicopathological significance of LETM1 expression as a prognostic determinant in head and neck squamous cell carcinoma (HNSCC). HNSCC samples from 176 patients were selected for immunohistochemical staining of LETM1 protein. Correlations between LETM1 overexpression and clinicopathological features of HNSCC were evaluated by Chi-squared tests and Fisher’s exact tests, and relationships between prognostic factors and patient survival were analyzed using Cox proportional hazards models. Our results demonstrated that the strongly positive rate of LETM1 protein was 65.3% in HNSCC, which was significantly higher than in either adjacent nontumor tissue (25.0%) or normal squamous epithelia (6.7%). LETM1 overexpression correlated with poor differentiation, presence of lymph node metastasis, advanced stage, absence of chemoradiotherapy, and 5-year disease-free survival and overall survival rates in HNSCC. Further analysis showed that high LETM1 expression, advanced stage, and nonchemoradiotherapy were significant independent risk factors for mortality in HNSCC. In conclusion, LETM1 plays an important role in the progression of HNSCC and is an independent poor prognostic factor for HNSCC.

scholarly journals 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

2011 ◽  
Vol 286 (32) ◽  
pp. 28444-28455 ◽  
Author(s):  
Markus Waldeck-Weiermair ◽  
Claire Jean-Quartier ◽  
Rene Rost ◽  
Muhammad Jadoon Khan ◽  
Neelanjan Vishnu ◽  
...  
Keyword(s):  
Leucine Zipper ◽  
Transmembrane Protein ◽  
Uncoupling Proteins ◽  
Ef Hand

The leucine zipper EF ‐hand containing transmembrane protein‐1 EF ‐hand is a tripartite calcium, temperature and pH sensor

2021 ◽  
Author(s):  
Qi‐Tong Lin ◽  
Rachel Lee ◽  
Allen L. Feng ◽  
Michael S. Kim ◽  
Peter B. Stathopulos
Keyword(s):  
Leucine Zipper ◽  
Transmembrane Protein ◽  
Ph Sensor ◽  
Ef Hand

Evi-2, a common integration site involved in murine myeloid leukemogenesis

1990 ◽  
Vol 10 (9) ◽  
pp. 4658-4666
Author(s):  
A M Buchberg ◽  
H G Bedigian ◽  
N A Jenkins ◽  
N G Copeland
Keyword(s):  
Leucine Zipper ◽  
Transmembrane Domain ◽  
Integration Site ◽  
Transmembrane Protein ◽  
Structural Features ◽  
Viral Integration ◽  
Integration Sites ◽  
Leukemia Viruses ◽  
Common Integration Site

BXH-2 mice have the highest incidence of spontaneous retrovirally induced myeloid leukemia of any known inbred strain and, as such, represent a valuable model system for identifying cellular proto-oncogenes involved in myeloid disease. Chronic murine leukemia viruses often induce disease by insertional activation or mutation of cellular proto-oncogenes. These loci are identified as common viral integration sites in tumor DNAs. Here we report on the characterization of a novel common viral integration site in BXH-2 myeloid leukemias, designated Evi-2. Within the cluster of viral integration sites that define Evi-2, we identified a gene that has the potential for encoding a novel protein of 223 amino acids. This putative proto-oncogene possesses all of the structural features of a transmembrane protein. Within the transmembrane domain is a "leucine zipper," suggesting that Evi-2 is involved in either homopolymer or heteropolymer formation, which may play an important role in the normal functioning of Evi-2. Interestingly, the human homolog of Evi-2 has recently been shown to be tightly linked to the von Recklinghausen neurofibromatosis locus, suggesting a role for Evi-2 in human disease as well.

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