Ask about this productRelated genes to: UQCRC1 Blocking Peptide
- Gene:
- UQCRC1 NIH gene
- Name:
- ubiquinol-cytochrome c reductase core protein 1
- Previous symbol:
- -
- Synonyms:
- D3S3191, QCR1, UQCR1
- Chromosome:
- 3p21.31
- Locus Type:
- gene with protein product
- Date approved:
- 1993-07-09
- Date modifiied:
- 2017-09-12
Related products to: UQCRC1 Blocking Peptide
Related articles to: UQCRC1 Blocking Peptide
- Gitelman syndrome (GS) is an autosomal recessive tubulopathy caused by SLC12A3gene mutations. While electrolyte disturbances are well-defined, the systemic metabolic consequences and underlying mechanisms remain unclear. This study investigated whether SLC12A3mutation drives mitochondrial dysfunction and consequent metabolic reprogramming in GS, utilizing a genetically homogeneous founder population with a homozygous SLC12A3p.C421F mutation. We conducted quantitative plasma proteomic analysis (directDIA) in wild-type (WT) and homozygous (HOM) individuals (n = 6/group) and established an isogenic SLC12A3p.C421F homozygous 293T cell model via CRISPR-Cas9. A series of functional assays were performed, including assessment of mitochondrial DNA copy number, membrane potential (JC-1), oxidative stress markers (SOD, MDA, ROS), lipid metabolism (lipid droplets, triglycerides, glycerol, cholesterol), NAD(H)/NADP(H) pools, intracellular ATP levels, enzymatic activities of all five mitochondrial respiratory chain complexes, extracellular acidification rate (ECAR), and expression of key oxidative phosphorylation proteins. Plasma proteomics revealed a significant downregulation of mitochondrial oxidative phosphorylation, TCA cycle, and fatty acid oxidation proteins in HOM individuals. In the cellular model, the mutation recapitulated this signature, showing reduced expression of core respiratory chain subunits (SDHA, UQCRC1, ATP5D). Functionally, HOM cells exhibited impaired activities of respiratory chain complexes I-V, reduced ATP content, and a compensatory increase in glycolytic flux (ECAR). This bioenergetic deficit was accompanied by diminished mtDNA copy number, dissipated mitochondrial membrane potential, elevated oxidative stress, and aberrant lipid metabolism (decreased lipid droplets and triglycerides). Notably, redox cofactor profiling showed a contracted NADP(H) pool alongside an expanded NAD(H) pool. Our integrated multi-omics and functional approach establishes a strong association between the SLC12A3 p.C421F mutation and a state of mitochondrial bioenergetic failure-characterized by impaired oxidative phosphorylation, an ATP deficit, and a compensatory metabolic shift towards glycolysis-in GS. The distinct NAD(H)/NADP(H) imbalance further indicates profound metabolic reprogramming. These findings extend the pathophysiological understanding of GS beyond a pure tubulopathy to a systemic disorder involving mitochondrial dysfunction, offering new mechanistic insights and potential therapeutic targets. - Source: PubMed
Publication date: 2026/09/21
Zhang HonghanZhao WenqianMa LanxinYang XueliGao JinghuaLiu XiaolingXie Y-GHu YingLuo HengHan Jian - Loin pain hematuria syndrome (LPHS) is characterized by chronic loin pain and hematuria without a urological cause. We hypothesized that rare genetic variants in genes impacting the glomerular filtration barrier (endothelial cells, glomerular basement membrane, or podocytes) may contribute to LPHS. - Source: PubMed
Publication date: 2026/08/14
Prasad BhanuSoliman Ahmed MGarg AartiSharma AditiSchott ClaraConnaughton DervlaLanktree Matthew B - The pathogenesis of diabetic kidney disease (DKD) is complex. Normoalbuminuric diabetic kidney disease (NADKD) is a special subtype of DKD that often progresses insidiously without detectable albuminuria, posing diagnostic and therapeutic challenges. Its pathogenesis remains unclear. Proteomic analysis of renal tissues may offer insights into its pathogenesis and identify biomarkers. - Source: PubMed
Publication date: 2026/08/26
Liu LuZhao YanLi YuanYang ChaonaWang MuxiYang MengyuanNiu MenghanXing Guolan - Mitochondrial dysfunction is a central pathogenic mechanism in Parkinson's disease (PD), particularly in genetic forms associated with respiratory chain impairment. Disease-modifying therapies capable of restoring neuronal bioenergetics while achieving non-invasive brain delivery remain lacking. This study investigated the therapeutic potential of an arginine-enriched penetratin-derived peptide (PenArg) in a genetic PD model carrying the UQCRC1 (p.Tyr314Ser) mutation. - Source: PubMed
Chang Jui-ChihYeh Cheng-YiLiu Kai-LiChao Yi-ChunLin Chin-HsienLiu Chin-San - Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system characterized by inflammatory demyelination, progressive neurodegeneration, and irreversible disability. While immune dysregulation initiates disease pathology, the molecular mechanisms linking chronic inflammation to mitochondrial dysfunction and oxidative stress remain incompletely understood. An integrative, multi-layered systems biology approach was applied to four independent RNA-sequencing datasets derived from MS white matter lesions, lesion-border microglia/macrophages, and Epstein-Barr virus-associated B cells. Differential gene expression analysis was combined with targeted prioritization of mitochondrial and oxidative stress-related genes using curated databases. Protein-protein interaction network construction, hub gene identification, Gene Ontology, and KEGG pathway enrichment analyses were performed to identify prioritized mitochondrial genes and enriched biological pathways. Independent validation was conducted using CNS-specific TNMplot expression profiling, and prognostic relevance was assessed through immunogenomic survival analysis. Structural and functional impacts of prioritized variants were evaluated using in silico pathogenicity prediction, protein stability analysis, secondary structure modeling, and three-dimensional structural assessment, including MutPred2 and HOPE analyses. Transcriptomic integration revealed consistent dysregulation of gene expression profiles across all datasets. Functional enrichment analyses identified mitochondrial oxidative phosphorylation as the most significantly enriched biological process, suggesting an association between altered mitochondrial respiratory pathways and MS-related molecular signatures. Network and enrichment analyses consistently prioritized UQCRC1 and COX4I1 as key mitochondrial hub genes, corresponding to core subunits of respiratory chain complexes III and IV, respectively. These genes were recurrently enriched across biological processes, cellular components, molecular functions, and neurodegeneration-related pathways. CNS-restricted validation confirmed their differential expression, while immunogenomic analysis demonstrated that higher expression levels were associated with improved overall survival. Variant-level analysis identified UQCRC1 (G235R, L197R) and COX4I1 (G155C, P152R) as deleterious substitutions predicted to destabilize protein structure, disrupt domain interactions, and impair electron transport efficiency. Functional predictions further indicated altered catalytic activity, metal binding, and structural integrity, supporting their potential functional relevance to mitochondrial biology. This study demonstrates that mitochondrial respiratory chain-related pathways, particularly those involving complexes III and IV, are consistently associated with the transcriptomic alterations observed in multiple sclerosis. UQCRC1 and COX4I1 emerged as prioritized mitochondrial hub genes supported by integrated transcriptomic, network, prognostic, and structural analyses. These findings provide evidence that mitochondrial bioenergetics and redox homeostasis may contribute to MS pathobiology and warrant further experimental investigation as potential biomarkers and therapeutic targets. - Source: PubMed
Publication date: 2026/08/19
Tarkina TatyanaAzanbayeva DinaraAlgazina TogzhanTouir GulnazKotlyarova TatyanaSavenok MarinaJetpisbayeva ZulfiyaBatpenova GulnarTsoy Natalya