MICU1

Last update 08 May 2025

Basic Info

Synonyms

ara CALC, Atopy-related autoantigen CALC, CALC

+ [8]

Introduction

Isoform that regulates mitochondrial calcium uniporter (MCU) in the skeletal muscle (By similarity). Compared to other isoforms, this isoform has higher affinity for calcium, promoting mitochondrial calcium uptake at lower calcium concentrations (By similarity). This allows a rapid response of mitochondrial metabolism and ensures sustained ATP production needed for resistance and strenuous exercise (By similarity). Calcium sensor of the mitochondrial calcium uniporter (MCU) channel, which senses calcium level via its EF-hand domains (PubMed:20693986, PubMed:23101630, PubMed:23747253, PubMed:24313810, PubMed:24332854, PubMed:24503055, PubMed:24560927, PubMed:26341627, PubMed:26903221, PubMed:27099988, PubMed:28615291, PubMed:30454562, PubMed:30638448, PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:32790952, PubMed:34463251, PubMed:36206740, PubMed:37036971, PubMed:37126688). MICU1 and MICU2 (or MICU3) form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium (PubMed:24560927, PubMed:26903221, PubMed:28615291, PubMed:32148862, PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:32790952, PubMed:36206740, PubMed:37036971, PubMed:37126688). At low calcium levels, MICU1 occludes the pore of the MCU channel, preventing mitochondrial calcium uptake (PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:37036971, PubMed:37126688). At higher calcium levels, calcium-binding to MICU1 and MICU2 (or MICU3) induces a conformational change that weakens MCU-MICU1 interactions and moves the MICU1-MICU2 heterodimer away from the pore, allowing calcium permeation through the MCU channel (PubMed:32494073, PubMed:32667285, PubMed:32762847). Also required to protect against manganese toxicity by preventing manganese uptake by MCU: mechanistically, manganese-binding to its EF-hand domains does not induce any conformational change, maintaining MCU pore occlusion (PubMed:30082385, PubMed:30403999). Also acts as a barrier for inhibitors of the MCU channel, such as ruthenium red or its derivative Ru360 (PubMed:37244260). Acts as a regulator of mitochondrial cristae structure independently of its ability to regulate the mitochondrial calcium uniporter channel (PubMed:31427612, PubMed:37098122). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22904319). Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (PubMed:16002733).

100 Clinical Results associated with MICU1

100 Translational Medicine associated with MICU1

0 Patents (Medical) associated with MICU1

1,033

Literatures (Medical) associated with MICU1

01 Aug 2025·Neural Networks

S4-KD: A single step spiking SiamFC+ + for object tracking with knowledge distillation

Article

Author: Xiang, Shuiying ; Zhang, Yahui ; Han, Yanan ; Liu, Wenzhuo ; Zhang, Tao ; Guo, Xingxing ; Yu, Licun ; Hao, Yue

Spiking neural networks (SNNs), which transmit information through binary spikes, have the advantages of high efficiency and low energy consumption. At present, the multiple time steps of SNNs can lead to increased latency and power consumption. To this end, we propose Single Step Spiking SiamFC+ + (S4), an improved single-step end-to-end direct training target tracking framework that compresses the time step to 1 by temporal pruning, using AlexNet as the backbone network. Experimental results show that, even when only a single time step is used, the tracking performance of the proposed S4 is still comparable to the original Spiking SiamFC+ +. Furthermore, we introduce the knowledge distillation to improve the performance of the proposed S4, which is called S4-KD for clarity. Three kinds of distillation loss functions are designed for the S4-KD. An artificial neural network model based on the AlexNet network serves as the teacher model, while the temporal-pruned S4 model acts as the student model for retraining. Experimental results show that the S4-KD tracker achieves higher performance on several tracking benchmarks. More specifically, on the OTB100 dataset, Precision and Success are 0.871 and 0.657 respectively, on the UAV123 dataset, Precision and Success are 0.766 and 0.603 respectively, and on the VOT2018 dataset, A, R, and EAO are 0.582, 0.370, and 0.278 respectively. In addition, the estimated energy consumption of the S4-KD is only 34.6 % of that of the original Spiking SiamFC+ +. To the best of our knowledge, the proposed S4-KD tracker surpasses all the existing SNN-based object tracking methods, achieving state-of-the-art performance. Our codes will be available at https://github.com/PSNN-xd/S4-KD.

01 Jul 2025·Cellular Signalling

GINS4 silencing mediates hepatocellular cancer cell proliferation, cycle and ferroptosis through POLE2

Article

Author: Wang, Congyu ; Song, Rui ; Xu, Zhe ; Yao, Jinni ; Yang, Huaicheng ; Zeng, Xiangrui ; Zhang, Zheng ; Yuan, Meng ; Liao, Heqiang

BACKGROUNDGINS4 has been identified as a regulator associated with multiple types of cancers. However, the effects of GINS4 on hepatocellular carcinoma (HCC) have not been reported.METHODSGINS4 expression in HCC was evaluated utilizing UALCAN database. The relationship between the expression of GINS4 and the survival probability of HCC patients was analyzed using Kaplan-Meier Plotter. Cell viability was evaluated by CCK8 assay and EDU assay. qRT-PCR and western blot were performed to examine GINS4 expression. The level of cell cycle was measured by flow cytometry and western blot. Fe²⁺ level and ferroptosis-related proteins were measured by corresponding kits and western blot. Lipid peroxidation was explored by C11 BODIPY 581/591 probe. STRING database and HDOCK database were performed to predict the binding of GINS4 to POLE2. Immunofluorescence and western blotting was adopted for assessing cell autophagy and mTOR signaling pathway. Ki67 and GPX4 levels were measured by immunohistochemistry. The expression levels of POLE2/PI3K/AKT were assessed by western blot.RESULTSThe data indicated that GINS4 expression was upregulated in HCC. Knockdown of GINS4 alleviated the proliferation and cycle and promoted ferroptosis of HuH7 cells. GINS4 was proved to bind to POLE2 and the silencing of GINS4 inhibited the expression of POLE2. GINS4 knockdown accelerated ferroptosis in HuH7 cells. POLE2 overexpression reversed the influences of GINS4 silencing on proliferation and cycle, and also ferroptosis. In addition, interference with GINS4 suppressed the activation of PI3K/AKT signaling via POLE2. In vivo experiments illustrated that GINS4 deletion suppressed HCC tumor growth, increased the GPX4 expression and restrained the Ki67 level, as well as reducing POLE2/PI3K/AKT signaling.CONCLUSIONGINS4 silencing suppressed proliferation and cycle while promoted ferroptosis in HCC cells by regulating PI3K/AKT signaling via binding to POLE2.

01 May 2025·International Journal of Biological Macromolecules

Synthesis, design, and cholinesterase inhibitory activity of novel 1,2,4-triazole Schiff bases: A combined experimental and computational approach

Article

Author: Sağlamtaş, Rüya ; Manap, Sevda ; Atalay, Abdurrahman ; Ekinci, Emel ; Tüzün, Burak ; Yüksek, Haydar ; Ortaakarsu, Ahmet Buğra ; Medetalibeyoğlu, Hilal

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is characterized by cholinergic dysfunction, necessitating the development of potent cholinesterase inhibitors for therapeutic intervention. In this research, a series of novel 1,2,4-triazole Schiff bases (S1-S8) was successfully synthesized and tested for their cholinesterase inhibitory activities both in vitro and in silico. 4-Hydroxy-3-methoxybenzaldehyde reacted with 4-methylbenzene sulfonyl chloride, then refluxed and recrystallized to form 4-formyl-2-methoxyphenyl 4-methyl benzenesulfonate, which combined with 4-amino-5-alkyl(aryl)-2,4-dihydro-3H-1,2,4-triazol-3-ones in acetic acid to yield Schiff bases. The synthesis yielded high-purity compounds with efficiency ranging from 87.5 % to 99.5 %, confirmed through IR, ¹H NMR, ¹³C NMR, and UV-Vis spectroscopy. The biological evaluation showed that S4 demonstrated the strongest inhibition of acetylcholinesterase (AChE) with an IC₅₀ of 3.00 μM, significantly outperforming rivastigmine (IC₅₀ = 8.95 μM) and galantamine (IC₅₀ = 29.5 μM). Additionally, S7 emerged as the most effective inhibitor of butyrylcholinesterase (BChE), with an IC₅₀ of 0.77 μM, comparable to rivastigmine (IC₅₀ = 0.62 μM) and far stronger than galantamine (IC₅₀ = 27.8 μM). The K_i values reinforced the selective inhibition properties, with S4 (1.04 ± 0.003 μM) and S7 (0.61 ± 0.001 μM) showing high affinity for AChE and BChE, respectively. Molecular docking studies identified crucial π-π interactions and hydrogen bonding between the triazole derivatives and key enzyme residues, contributing to their high inhibitory potency. These interactions were further validated through molecular dynamics simulations, which confirmed the stability of the S4 and S7 complexes with AChE and BChE over extended periods. Computational analysis, including FMO studies, supported the experimental data, showing that HOMO-LUMO energy gaps significantly influenced the compounds' reactivity, stability, and inhibitory profiles. Overall, the study presents strong evidence that these novel 1,2,4-triazole Schiff bases possess potent and selective cholinesterase inhibition, notably S4 for AChE and S7 for BChE. These results suggest that these novel compounds have significant potential as selective cholinesterase inhibitors, particularly for Alzheimer's disease, warranting further in vivo studies.

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MICU1

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