Ask about this productRelated genes to: NDUFA9 Blocking Peptide
- Gene:
- NDUFA9 NIH gene
- Name:
- NADH:ubiquinone oxidoreductase subunit A9
- Previous symbol:
- NDUFS2L
- Synonyms:
- SDR22E1, CI-39k, COQ11
- Chromosome:
- 12p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1997-12-17
- Date modifiied:
- 2019-03-13
Related products to: NDUFA9 Blocking Peptide
Related articles to: NDUFA9 Blocking Peptide
- Primary coenzyme Q10 (CoQ10) deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In humans, at least 10 genes (, to ) are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status and present as primary CoQ10 deficiency. Furthermore, the genes and , whilst not part of the , to gene sequence, have also been shown to have a crucial role in CoQ10 biosynthesis. A major problem in treating primary CoQ10 deficiencies is the poor bioavailability of supplemental CoQ10, both in terms of lack of absorption from the digestive tract and inability to cross the human blood-brain barrier. Bypass strategies aim to circumvent this problem by using more bioavailable precursor analogues that can enter the cell and be incorporated into the CoQ10 synthesis pathway downstream of the affected enzyme, examples being 4-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid or vanillic acid, which, in contrast to CoQ10, are small, water-soluble molecules. In this article, we have, therefore, reviewed potential bypass mechanisms for primary CoQ10 deficiencies, PDSS1, PDSS2 to COQ10, together with NDUFA9 and HPDL, using such precursors. Most of the published data relating to the bypass therapy of primary CoQ10 deficiency is derived from cell lines or animal models, and few human studies have so far been undertaken. In addition, further research is required to investigate the potential mechanisms by which bypass compounds such as 4-HB may access the human blood-brain barrier (BBB), for example, using in vitro co-culture BBB model systems incorporating CoQ10-deficient neurons. Overall, the objective of this article is, therefore, to systematically review the available data for each of the primary CoQ10 deficiencies, PDSS1, PDSS2 to COQ10 together with NDUFA9 and HPDL, in particular to identify the clinical potential of such studies. - Source: PubMed
Publication date: 2026/04/15
Mantle DavidCufflin NeveHargreaves Iain P - NSCLC remains a primary contributor to cancer-related mortality. This study comprehensively elucidates the expression and the functional role of NDUFA9 in NSCLC pathogenesis. Our initial bioinformatic analyses, drawing from TCGA and single-cell RNA sequencing data, revealed a significant upregulation of NDUFA9 expression within NSCLC tumor tissues and cancer cell populations, correlating with unfavorable clinicopathological indicators, including advanced pathological T stage, male gender, smoking history, and diminished overall survival. Furthermore, NDUFA9 was distinctly enriched in proliferating cancer cells and malignant epithelial cells across diverse metastatic sites. Experimental validation confirmed NDUFA9's heightened mRNA and protein expression in both locally-treated NSCLC patient tissues and various NSCLC cell types. Functionally, NDUFA9 shRNA or knockout compromised mitochondrial function in NSCLC cells. This impairment was evidenced by a reduced oxygen consumption rate, diminished mitochondrial complex I activity, decreased ATP production, mitochondrial depolarization, reduced mtDNA contents, and an augmented generation of ROS. Concomitantly, NDUFA9 depletion significantly suppressed key malignant phenotypes, including cell proliferation and migration, while inducing apoptosis in NSCLC cells. Conversely, NDUFA9 overexpression in NSCLC cells enhanced mitochondrial function and promoted malignant cellular phenotypes. NDUFA9 was identified as a positive regulator of the Akt-mTOR signaling pathway; its depletion inhibited, and its overexpression enhanced, mTOR kinase activity and the phosphorylation of Akt and S6K in primary NSCLC cells. Bioinformatics predictions, subsequently validated experimentally, established YY1 as a pivotal transcription factor directly binding to and upregulating NDUFA9 expression in NSCLC tissues and cells. Finally, in vivo xenograft studies demonstrated that NDUFA9 silencing suppressed tumor growth, corroborating the in vitro findings by inhibiting mitochondrial function, proliferation, Akt-mTOR activation, and inducing apoptosis within tumor tissues. Thus, NDUFA9 is a crucial regulator of mitochondrial metabolism and malignant progression in NSCLC, driven by YY1-mediated transcriptional control. - Source: PubMed
Publication date: 2026/04/21
Yan YuboZhao YugeTang JunWang XiwenZhao JungangYang Yingnan - Fatty liver hemorrhagic syndrome (FLHS) is a nutrition-related metabolic disorder in laying hens characterized by excessive hepatic lipid accumulation and hemorrhagic lesions, leading to reduced productivity and increased mortality. However, the regulatory mechanisms linking mitochondrial dysfunction to hepatic lipid metabolism remain unclear. This study investigated the role of SIRT3 in modulating mitochondrial fatty acid oxidation during FLHS progression. An in vivo FLHS model was established by feeding laying hens with a high-energy, low-protein (HELP) diet, and an in vitro hepatic steatosis model was induced by free fatty acid (FFA) treatment in primary hepatocytes. Both models exhibited pronounced lipid accumulation in hepatic cells and altered hepatocellular injury-related parameters, which were associated with mitochondrial dysfunction and impaired fatty acid oxidation. Mechanistically, hepatic tissues and hepatocytes showed suppression of the SIRT3-AMPKα-PGC-1α signaling cascade, accompanied by reduced expression of mitochondrial biogenesis markers (NRF1, TFAM), impaired respiratory chain components (NDUFA9, SDHA, UQCRC1, COX4I1, ATP5B), and decreased transcription of fatty acid oxidation-related genes (PPARα, ACOX1, CPT1A, CPT2, ACADL, ACADM). Pharmacological activation of SIRT3 with AR-C17 restored AMPKα-PGC-1α signaling, enhanced mitochondrial biogenesis and respiratory function, and promoted fatty acid oxidation, thereby alleviating lipid accumulation in hepatocytes in both models. Collectively, these results demonstrate that SIRT3 is a key metabolic regulator maintaining mitochondrial oxidative function and lipid homeostasis in laying hens. Targeted activation of SIRT3 may provide a novel nutritional strategy for preventing or ameliorating FLHS and related metabolic disturbances in poultry production. - Source: PubMed
Publication date: 2026/04/07
Cao PanpanChen JinyanZeng ChunHu YangYuan JianyunGuo XiaoquanCao HuabinZhang CaiyingZhuang YuHu Guoliang - Despite successful immuno-oncology therapies in other cancers, they largely failed in glioblastoma(GBM). Here, natural killer (NK) cells from glioma patients show impaired oxidative phosphorylation and mitochondrial complex I activity. Multiomics profiling identified complex I subunit NDUFA9 as a critical mediator of NK cell metabolic fitness. Abundance of NDUFA9+ NK cells informed patient outcome. Ndufa9 knockout in NK cells compromised mitochondrial function, anti-tumor efficacy, and memory-like phenotype of NK cells by triggering a metabolic reprogramming toward glutamine dependence. Decreased α-ketoglutarate(α-KG)/succinate ratio in Ndufa9-deficient NK cells mediated widespread epigenetic reprogramming through inducing transcriptionally repressive histone mark H3K27me3 on key immune function genes. Resveratrol-mediated NDUFA9 activation or its overexpression enhanced NK cell anti-GBM function by restoring complex I activity. Together, these findings reveal the critical role of mitochondrial complex I activity in NK cells and highlight its potential as an actionable target to enhance NK cell-based immunotherapy for GBM patients. - Source: PubMed
Publication date: 2026/04/07
Zhou NianxinFei FanTang LinZhang PeidongWang WeiZheng BohaoShen QiuhongYue JingHuang LiangDu YiweiLiao XiaolingOuyang LiangYuan GangRich Jeremy NZhou ShengtaoZhao Linjie - High-altitude cerebral edema (HACE) is a type of lethal neurological emergency, whose underlying pathogenic mechanisms and core therapeutic targets remain largely unelucidated to date. Optimized Xueyu Jingshen formula (OXJF) has been shown to exert definite clinical efficacy in the intervention of HACE, whereas the underlying molecular mechanisms remain to be systematically and deeply explored. - Source: PubMed
Publication date: 2026/02/13
Bai JinrongXie NaHou YaYan JieruiChen MinYu ShufuMeng XianliZhang YiWang Xiaobo