Ask about this productRelated genes to: EFHA2 antibody
- Gene:
- MICU3 NIH gene
- Name:
- mitochondrial calcium uptake family member 3
- Previous symbol:
- EFHA2
- Synonyms:
- DKFZp313A0139
- Chromosome:
- 8p22
- Locus Type:
- gene with protein product
- Date approved:
- 2004-10-13
- Date modifiied:
- 2015-11-18
Related products to: EFHA2 antibody
Related articles to: EFHA2 antibody
- The role of sodium-glucose cotransporter-1 (SGLT1) in mitochondrial biology function remains unclear. This study aimed to investigate the causal association between SGLT1 inhibition and mitochondrial biology function via Mendelian randomization (MR) analysis. - Source: PubMed
Publication date: 2026/03/13
Fan GangQu Zi-Han - Neurological disorders are linked to mitochondrial dysfunction and calcium overload. Mitochondrial calcium uptake is mediated by the mitochondrial calcium uniporter (mtCU), regulated by MICU1, which can be either homodimerized or heterodimerized with MICU2 or MICU3. Though MICU2 is scarce in the adult brain, MICU2 loss in patients leads to a neurodevelopmental disorder. We hypothesized that MICU2 is required for developmental calcium signaling and neuronal migration. MICU2 is present in the developing mouse brain but disappears by maturation, contrasting with other mtCU subunits that increase. MICU2 loss in mice does not affect cytoplasmic calcium but augments the mitochondrial matrix calcium rise in primary cortical neurons, leading to neuronal overmigration in the cortex and behavioral changes at 2 but not 12 months. Consistently, mitochondrial calcium uptake is not significantly affected in the adult animal cortex. MICU2-deficient patient fibroblasts copy the mitochondria-confined calcium alteration in developing neurons. Thus, MICU2 is important during neurodevelopment, likely by regulating the mtCU, and is eliminated by brain maturation. - Source: PubMed
Publication date: 2025/11/20
Berezhnaya ElenaCartes-Saavedra BenjamínSingh RaghavendraRodríguez-Prados MacarenaReiner OrlyAlkuraya Fowzan SHajnóczky György - More and more studies have shown that mitochondria play a key role in the pathogenesis of sepsis. However, the pathogenesis of sepsis is complex, and there are ethical and implementation challenges in conducting large-scale randomized controlled trials. Mendelian randomization (MR) analysis selects genetic variants as instrumental variables based on genome-wide association studies (GWAS) to infer causal relationships, which can avoid traditional confounding factors. The data of this study were sourced from the IEU OpenGWAS database. The GWAS summary data of 66 mitochondrial functional proteins (MPs) and 5 types of sepsis and their subtypes were included. The "TwoSampleMR" R package was used for analysis. Five methods, including the inverse variance weighted (IVW) method, were used for causal effect analysis. Horizontal pleiotropy and heterogeneity were detected, and sensitivity and reverse association analyses were carried out. The results showed that MICU3, GRPEL1, HTRA2, ISCU, NDUFS4, MCEE, ES1, and LONP1 were protective factors for sepsis, while Grx2, MRM3, and PheRS were risk factors. Among them, MICU3 was strongly correlated with sepsis (28-day death in ICU), and Grx2 was strongly correlated with sepsis (28-day death). This study used 5 MR analysis methods to explore the causal relationships between 66 MPs and 5 types of sepsis and their subtypes for the first time. It was found that some MPs were potential protective factors for sepsis or its subtypes, while some were risk factors. These risk factor MPs may have time-dependent bidirectional effects in the regulation of mitochondrial function in sepsis. This study provides new evidence for elucidating the role of these MPs in the pathophysiology of sepsis, which helps to gain an in-depth understanding of the pathogenesis of sepsis and also lays the foundation for exploring future treatment strategies. - Source: PubMed
Zheng BochaoWang YingdanJi SuhaoLiu Ben - Mitochondrial matrix Ca concentration ([Ca]) is theorized to be an essential regulator of mitochondrial metabolism by positively regulating key mitochondrial dehydrogenases. However, ablation or functional inhibition of the mitochondrial calcium uniporter channel (mtCU) fails to significantly perturb basal metabolism and is largely phenotypically silent in the absence of stress. This begs the question, what are the primary molecular mechanisms regulating calcium-dependent changes in metabolism? The primary function of MICU proteins (MICU1, MICU2, and MICU3) is reported to be gatekeeping of the mtCU and regulating mitochondrial Ca uptake. Here, we demonstrate that MICU proteins function in coordination to impart Cadependent regulation to FADH-dependent mitochondrial dehydrogenases through metabolon formation independent of the mtCU and [Ca]. Our results demonstrate that MICU proteins differentially localize to mitochondrial microdomains and form heterodimers and interactomes in response to intermembrane space Ca binding their respective EF-hand domains. Utilizing an equimolar expression platform coupled with unbiased proteomics we reveal unique interactomes for MICU1/2 versus MICU1/3 heterodimers and demonstrate that MICU proteins control coupling of Mitochondrial Glycerol-3-Phosphate Dehydrogenase with Succinate Dehydrogenase/Complex II and impart Cadependent changes in activity. We propose that MICU-mediated mitochondrial metabolons are a fundamental system facilitating matching of mitochondrial energy production with cellular demand and is the primary physiological Ca signaling mechanism regulating homeostatic energetics - not mtCU-dependent changes in [Ca]. - Source: PubMed
Publication date: 2025/06/26
Cohen Henry MGottschalk BenjaminChoya-Foces CarmenChathoff AdamWilkinson AnyaGarbincius Joanne FJohnson AdysonStevens Tyler LHowe Jordan EMegill EmilyNgo JennyferTomar DhanendraSnyder Nathaniel WGraier Wolfgang FElrod John W - Ischemic heart disease is a leading cause of mortality and disability worldwide among cardiovascular conditions. Myocardial ischemia-reperfusion injury (MIRI) occurs following percutaneous coronary intervention, during which neutrophils generate neutrophil extracellular traps (NETs) in response to injury. This study aims to elucidate the mechanisms underlying NET activation and its impact on MIRI. Sham and MIRI rat models were established. Various techniques, including enzyme-linked immunosorbent assay, hematoxylin and eosin staining, Masson staining, and transmission electron microscopy, were used to assess endothelial cell injury and myocardial tissue inflammation. Immunofluorescence was employed to evaluate NET activation in tissues, peripheral blood neutrophils, and protein colocalization. MitoTracker and ER-Tracker staining were conducted to assess the formation of mitochondria-associated membranes (MAMs). Extracted NETs were applied to conduct microvascular endothelial cell tube formation assay and flow cytometry. RNA-sequencing and immunoprecipitation-mass spectrometry were applied to determine the key regulators. Flow cytometry and Western blot were used to assess Ca and mitophagy levels in neutrophils. Deoxyribonuclease I, NET inhibitor, was injected into MIRI rats to evaluate the in vivo effects of NET modulation on MIRI severity. MIRI was often accompanied by cardiac microvascular endothelial cell (CMEC) injury and inflammation. Lactate mediated H3K18 lactylation at the MICU3 promoter in neutrophils, enhancing its transcription and leading to elevated MICU3 levels. Besides, lactate also promoted the interaction between MICU3 and AASR1, stabilizing MICU3 through lactylation. Up-regulated MICU3 interacted with VDAC1, facilitating MAM formation, excessive Ca uptake, mitochondrial dysfunction, mitophagy activation, and NET activation. Elevated NET level exacerbated CMEC dysfunction, further aggravating MIRI. Lactate-driven MICU3 transcriptional activation and stabilization facilitates NET formation, contributing to MIRI development. - Source: PubMed
Publication date: 2025/05/30
Zhang HongruLiu LeiShen ChuchuJiang XinxueLiu JingChen JingXu SenleiMo Yanfei