LETM1

Last update 08 May 2025

Basic Info

Synonyms

LETM1, leucine zipper and EF-hand containing transmembrane protein 1, Leucine zipper-EF-hand-containing transmembrane protein 1

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Introduction

Plays an important role in maintenance of mitochondrial morphology and in mediating either calcium or potassium/proton antiport (PubMed:18628306, PubMed:19797662, PubMed:24344246, PubMed:24898248, PubMed:29123128, PubMed:32139798, PubMed:36055214, PubMed:36321428). Mediates proton-dependent calcium efflux from mitochondrion (PubMed:19797662, PubMed:24344246, PubMed:29123128). Functions also as an electroneutral mitochondrial proton/potassium exchanger (PubMed:24898248, PubMed:36055214, PubMed:36321428). Crucial for the maintenance of mitochondrial tubular networks and for the assembly of the supercomplexes of the respiratory chain (PubMed:18628306, PubMed:36055214). Required for the maintenance of the tubular shape and cristae organization (PubMed:18628306, PubMed:32139798).

100 Clinical Results associated with LETM1

100 Translational Medicine associated with LETM1

0 Patents (Medical) associated with LETM1

148

Literatures (Medical) associated with LETM1

01 Apr 2025·FEBS Letters

The apo LETM1 F‐EF‐hand adopts a closed conformation that underlies a multi‐modal sensory role in mitochondria

Article

Author: Colussi, Danielle M. ; Lin, Qi‐Tong ; Stathopulos, Peter B.

Leucine zipper EF‐hand containing transmembrane protein‐1 (LETM1) plays a critical role in mitochondrial function, with haploinsufficiency linked to Wolf‐Hirschhorn syndrome. Here, we present the solution NMR structure of the calcium (Ca2+)‐depleted LETM1 EF‐hand domain, revealing a closed conformation facilitated by a distinct F1‐helix pivot rather than decreased interhelical angle. Further, we observe regiospecific unfolding in response to hot and cold denaturation and show H662 has a pKa in‐line with physiological pH fluctuations. Finally, we demonstrate Ca2+‐dependent transient interactions between the EF‐hand and other LETM1 or GHITM protein domains. Collectively, our data reveal the apo‐to‐holo structural dynamics and mechanisms underlying the multi‐modal sensing by the LETM1 EF‐hand domain, highlighting its role as an adaptable regulatory element within the mitochondrial matrix.

01 Feb 2025·Biomedicine & Pharmacotherapy

Compound K promotes thermogenic signature and mitochondrial biogenesis via the UCP1-SIRT3-PGC1α signaling pathway

Article

Author: Jeong, Jiho ; Chun, Sungkun ; Oh, Jung-Mi ; Kim, Geonhyeong

Compound K (CK), an active ingredient in ginseng, has anti-cancer, anti-inflammatory, and antioxidant properties. However, its effects on thermogenesis and mitochondrial dynamics in white adipose tissue (WAT) adipocytes are not well understood. This study explores CK's impact on thermogenesis and mitochondrial metabolism in cold-exposed mice and mouse stromal vascular fraction (SVF) cells. CK increased the expression of UCP1 and other brown/beige adipocyte markers (Cd137, Cytb, Letm1, Pgc1α, Prdm16, Tbp1, Tbx1, Uqcrc1) and mitochondrial biogenesis/dynamics factors (Cidea, Cox8b, Cycs, Dio2, Drp1, Fis1, Fgf21, Nrf1, Sirt3, Tfam) in 3T3-L1/iWAT SVF cells. CK enhanced mitochondrial respiration, reduced mitochondrial ROS levels, and restored MMP in iWAT SVF cells, leading to the differentiation of WAT into beige adipocytes, and that was also observed in cold-exposed subcutaneous tissue. CK administration to cold-exposed mice reduced fat droplet size and increased the number of mitochondria. Additionally, CK stimulated non-shivering thermogenesis, indicated by the upregulation of thermogenic and mitochondrial division proteins. The browning effect of CK was nullified by SIRT3 knockdown, suggesting that CK induces beige remodeling of WAT by regulating mitochondrial dynamics and SIRT3 expression. These findings suggest CK's potential as a therapeutic agent for obesity and metabolic disorders that promotes the transformation of WAT into a metabolically active beige phenotype.

01 Jan 2025·Molecular and Cellular Endocrinology

Status of sperm mitochondrial functions and DNA methylation in infertile men with clinical varicocele before and after treatment

Article

Author: Kothari, Priyank ; Pawar, Prakash ; Goankar, Reshma ; Singh, Dipty ; Tandon, Deepti ; Arya, Deepshikha ; Gajbhiye, Rahul

Varicocele has been associated with reduced male fertility potential. Treatment modalities for varicocele improve semen parameters, yet more than 50% of cases remain infertile. Varicocele-induced heat and hypoxia stress may affect sperm mitochondrial functions, possibly leading to aberrant epigenetic modifications. This study includes 30 fertile men and 40 infertile men with clinical varicocele. The effect of varicocele treatment (antioxidant supplementation and or varicocelectomy) was evaluated after 3 months of treatment. Mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (iROS) were measured by flow cytometry using JC-1 and DCFDA, respectively. mtDNA copy number and deletions were determined by PCR. DNA methylation was analysed by pyrosequencing. Present investigations suggest that infertile men with varicocele have abnormal semen parameters; significantly low MMP, high iROS, and high mtDNA copy number. Semen parameters were improved in a subset of men of both the treatment modalities; however, it was noted that varicocelectomy helped better in improving sperm parameters compared to antioxidant treatment. Both treatment modalities helped in reducing iROS and mtDNA copy number significantly; however, they were noneffective in improving MMP. Altered DNA methylation at mitochondria D loop and mitochondrial structure and function genes UQCRC2, MIC60, TOM22, and LETM1 (promoter region) were observed in varicocele group. The DNA methylation levels were restored after varicocele treatment; however, the restoration was not consistent at all CpG sites. Both the treatment modalities helped in restoring the altered DNA methylation levels of mitochondrial genes but the restoration is nonhomogeneous across the studied CpG sites.

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LETM1

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