Ask about this productRelated genes to: FOXRED1 Blocking Peptide
- Gene:
- FOXRED1 NIH gene
- Name:
- FAD dependent oxidoreductase domain containing 1
- Previous symbol:
- -
- Synonyms:
- H17
- Chromosome:
- 11q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 2006-02-03
- Date modifiied:
- 2016-06-08
Related products to: FOXRED1 Blocking Peptide
Related articles to: FOXRED1 Blocking Peptide
- Developmental and epileptic encephalopathy (DEE) is a severe neurological disorder. Biallelic mutations in the nuclear-encoded mitochondrial chaperone gene FOXRED1, a specific assembly factor for complex I, cause mitochondrial dysfunction; however, their role in DEE pathogenesis remains unexplored. Clinical data and peripheral blood mononuclear cells (PBMCs) were obtained from two patients with compound heterozygous FOXRED1 mutations (c.850T>C (p.C284R)/c.1054C>T (p.R352W) and c.1054C>T (p.R352W)/c.3dup (p.I2Dfs*35) and age-matched controls. Mitochondrial phenotyping, included complex I activity, mitochondrial respiration stress test, membrane potential, intracellular ROS, and NAD/NADH ratio, were performed. Both patients exhibited early-onset refractory seizures, basal ganglia lesions, hyperlacticemia, and developmental regression. FOXRED1 mutations resulted in 50% reduction in complex I activity, dissasembly of complex I, mitochondrial depolarization, oxidative stress, and NAD/NADH imbalance. Niacin restored the NAD/NADH ratio in vitro, while clinical supplementation reduced blood lactate levels, suggesting it may be a potential therapeutic option. - Source: PubMed
Publication date: 2025/12/16
Pan CunhuiZhu RuoweiHuang XiDuan HaolinWu TenghuiWang XiaoleDing YingChen ChenHe FangPeng JingYin FeiLou XiaotingYang Li - Obesity has been identified as an independent risk factor for gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma (EAC). Oxidative stress and inflammation driven by chronic GERD are the main causes of the tumorigenesis of EAC, but the underlying mechanism remains elusive. Here, the inflammation-upregulated E3 ligase, tripartite motif 15 (TRIM15), is identified as a key driver of obesity-associated EAC. TRIM15 promotes the degradation of YY2 is demonstrated through the ubiquitin-proteasome system, which in turn dysregulates lipid metabolism and enhances the proliferation of EAC cells. Furthermore, YY2 transcriptionally is shown that increases FOXRED1 expression. FOXRED1 is subsequently identified as an essential effector for the TRIM15-induced dysregulation of lipid and energy metabolism in EAC cells. Thus, a novel obesity-associated TRIM15/YY2/FOXRED1 axis is identified that contributes to the proliferation of EAC. Given that lipid metabolism regulates ferroptosis by controlling cellular processes associated with phospholipid peroxidation. The TRIM15/YY2/FOXRED1 axis demonstrates that it modulates SLC3A2 expression via the mTOR/c-MYC pathway, thereby regulating GPX4 levels to influence EAC sensitivity to ferroptosis-inducing compounds and proposing a therapeutic strategy for EAC. - Source: PubMed
Publication date: 2025/11/14
Wang HaohuiYang ChongLuo DayuanLiu PingtingZeng ZhenPeng WeilinPeng DongziSu HaoXiao XiaoxiongWang HaiqinJin Xin - To analyze the clinical characteristics, genetic features and prognosis of infantile epileptic spasms syndrome (IESS) associated with mitochondrial gene variants. A case-series study was conducted, including 18 children diagnosed with mitochondrial gene variant-associated IESS at the Department of Pediatrics, Xiangya Hospital of Central South University from June 2016 to June 2025. General data, clinical manifestations, laboratory findings and treatment outcomes were systematically analyzed. Among the 18 children, 11 were boys, 7 were girls, the age of seizure onset was 6 (3, 9) months. Elevated lactate level was found in 7 children. Neuroimaging of magnetic resonance imaging revealed cerebral atrophy in 10 cases, and basal ganglia, thalamic, or midbrain lesions in 3 cases. Genetic testing identified 12 pathogenic genes, including mitochondrial protein synthesis-related genes: AFG3L2 (4 cases), PARS2 (3 cases), RARS2 (1 case), MIPEP (1 case), and PTCD3 (1 case); respiratory chain enzyme complex-related genes: FOXRED1 (2 cases), NDUFS7 (1 case), MT-ND1 (1 case), and MT-ATP6 (1 case); and other mitochondrial-related genes: POLG (1 case), COQ4 (1 case), and PDHA1 (1 case). ACTH or prednisone therapy was administered in 14 children, with 5 achieving spasm control for ≥28 d spasm freedom and resolution of hypsarrhythmia on electroencephalogram. Ketogenic diet therapy was used in 4 children, and effective in 1 case with the PDHA1 gene variant. Fourteen patients exhibited drug-resistant epilepsy requiring ≥2 antiseizure medications. At a follow-up of 3.0 (1.5, 4.3) years, 3 children died. Among 12 children ≥3 years of age, modified Rankin scale (mRS) scores demonstrated 1 case with favorable outcomes (mRS ≤2 score) and 11 with poor outcomes (mRS >2 score). s Mitochondrial gene variants in IESS mainly involve mitochondrial respiratory chain enzyme complexes and protein synthesis pathways, typically manifesting as drug-resistant epilepsy with poor prognosis. Elevated lactate levels combined with cerebral atrophy or basal ganglia lesions may aid diagnosis. - Source: PubMed
Wu T HLi RPan ZZhang Z WPeng J - Mitochondrial defects can lead to cardiomyopathies, which can be particularly severe in children. However, many cases of pediatric cardiomyopathy have no known etiology. To address this, we sought to explore if mitochondrial genome defects might be a contributor, as this could offer insights into disease mechanisms and guide targeted interventions. We first sequenced cardiomyopathy-related genes in twenty-seven pediatric patients diagnosed with primary non-syndromic cardiomyopathy and performed whole mtDNA sequencing in both patients and thirty-one healthy controls. The initial sequencing identified pathogenic variants in seven patients but subsequent mtDNA sequencing revealed additional insights. Specifically, a variant in FOXRED1, encoding FAD-dependent oxidoreductase domain-containing protein-1 which functions in mitochondrial complex I stability, and another variant in cytochrome c oxidase-I, MT-CO1, crucial for aerobic metabolism, were identified in two siblings with hypertrophic cardiomyopathy. In another case with hypertrophic cardiomyopathy, a variant in cytochrome b, MT-CYB, is likely a key factor in the abnormal contraction of cardiac muscle contraction. Furthermore, a novel 12 S rRNA variant was found in a patient with left ventricular non-compaction, and this offers a promising explanation for the pathogenesis, given the gene's high expression in the left ventricle. Taken together, mtDNA variants act synergistically with others, potentially disrupting myocardial bioenergetics. - Source: PubMed
Publication date: 2025/05/14
Temena M ArdaGokalp Ebru ErzurumluogluSusam EzgiCinar DuyguKiztanir HikmetKosger PelinAras Beyhan DurakArtan SevilhanCilingir Oguz
- Source: PubMed