PTPMT1

更新于：2025-05-07

基本信息

别名

DUSP23、MOSP、Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1

+ [6]

简介

Lipid phosphatase which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG) (By similarity). PGP is an essential intermediate in the biosynthetic pathway of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle (By similarity). Has also been shown to display phosphatase activity toward phosphoprotein substrates, specifically mediates dephosphorylation of mitochondrial proteins, thereby playing an essential role in ATP production (By similarity). Has probably a preference for proteins phosphorylated on Ser and/or Thr residues compared to proteins phosphorylated on Tyr residues (By similarity). Probably involved in regulation of insulin secretion in pancreatic beta cells (By similarity). May prevent intrinsic apoptosis, probably by regulating mitochondrial membrane integrity (PubMed:24709986).

关联

项与 PTPMT1 相关的药物

Alexidine dihydrochloride

靶点

PTPMT1

作用机制

PTPMT1 inhibitors

在研机构

Emory University

原研机构-

在研适应症

肺癌

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PTPMT1 相关的临床结果

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100 项与 PTPMT1 相关的转化医学

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0 项与 PTPMT1 相关的专利（医药）

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241

项与 PTPMT1 相关的文献（医药）

2025-02-03·Brain

Biallelic PTPMT1 variants disrupt cardiolipin metabolism and lead to a neurodevelopmental syndrome

Article

作者: Abdel-Hamid, Mohamed S ; Vandrovcova, Jana ; Heales, Simon J R ; Prudent, Julien ; Pope, Simon A S ; Maroofian, Reza ; Labrum, Robyn ; Chronopoulou, Efstathia ; Houlden, Henry ; Falabella, Micol ; Taylor, Robert W ; Patel, Nina ; Taanman, Jan-Willem ; Tabara, Luis Carlos ; Tilokani, Lisa ; Oktay, Yavuz ; Hanna, Michael G ; Macken, William L ; Woodward, Cathy E ; Hiz, Semra ; Sonmezler, Ece ; Pizzamiglio, Chiara ; Lu, Shanti ; Pierre, Germaine ; Horvath, Rita ; Lochmuller, Hanns ; Flannery, Padraig J ; Alston, Charlotte L ; Zaki, Maha S ; Pitceathly, Robert D S ; Hammadi, Dania B H ; Munro, Benjamin

AbstractPrimary mitochondrial diseases (PMDs) are among the most common inherited neurological disorders. They are caused by pathogenic variants in mitochondrial or nuclear DNA that disrupt mitochondrial structure and/or function, leading to impaired oxidative phosphorylation (OXPHOS). One emerging subcategory of PMDs involves defective phospholipid metabolism. Cardiolipin, the signature phospholipid of mitochondria, resides primarily in the inner mitochondrial membrane, where it is biosynthesized and remodelled via multiple enzymes and is fundamental to several aspects of mitochondrial biology. Genes that contribute to cardiolipin biosynthesis have recently been linked with PMD. However, the pathophysiological mechanisms that underpin human cardiolipin-related PMDs are not fully characterized.Here, we report six individuals, from three independent families, harbouring biallelic variants in PTPMT1, a mitochondrial tyrosine phosphatase required for de novo cardiolipin biosynthesis. All patients presented with a complex, neonatal/infantile onset neurological and neurodevelopmental syndrome comprising developmental delay, microcephaly, facial dysmorphism, epilepsy, spasticity, cerebellar ataxia and nystagmus, sensorineural hearing loss, optic atrophy and bulbar dysfunction. Brain MRI revealed a variable combination of corpus callosum thinning, cerebellar atrophy and white matter changes.Using patient-derived fibroblasts and skeletal muscle tissue, combined with cellular rescue experiments, we characterized the molecular defects associated with mutant PTPMT1 and confirmed the downstream pathogenic effects that loss of PTPMT1 has on mitochondrial structure and function. To further characterize the functional role of PTPMT1 in cardiolipin homeostasis, we created a ptpmt1 knockout zebrafish. This model had abnormalities in body size, developmental alterations, decreased total cardiolipin levels and OXPHOS deficiency.Together, these data indicate that loss of PTPMT1 function is associated with a new autosomal recessive PMD caused by impaired cardiolipin metabolism, highlighting the contribution of aberrant cardiolipin metabolism towards human disease and emphasizing the importance of normal cardiolipin homeostasis during neurodevelopment.

2024-12-01·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Micropeptide MPM regulates cardiomyocyte proliferation and heart growth via the AKT pathway

Article

作者: Chen, Hua-Xing ; Zhuang, Shi-Mei ; Xie, Peng-Peng ; Zhang, Wei ; Lin, Yi-Fang ; Huang, Jie-Yi ; Ma, Yan-Zhen ; Li, Lan-Qi ; Zhu, Ying

The role of micropeptide in cardiomyocyte proliferation remains unknown. We found that MPM (micropeptide in mitochondria) was highly expressed in cardiomyocytes. Compared to MPM^+/+ mice, MPM knockout (MPM^-/-) mice exhibited reduction in left ventricular (LV) mass, myocardial thickness and LV fractional shortening. RNA-sequencing analysis in H9c2, a rat cardiomyocyte cell line, identified downregulation of cell cycle-promoting genes as the most significant alteration in MPM-silencing cells. Consistently, gain- and loss-of-function analyses in H9c2 cells revealed that cardiomyocyte proliferation was repressed by silencing MPM but was promoted by overexpressing MPM. Moreover, the cardiomyocytes in the hearts of MPM^-/- mice displayed reduced proliferation rates. Mechanism investigations disclosed that MPM is crucial for AKT activation in cardiomyocytes. We also identified an interaction between MPM and PTPMT1, and found that silencing PTPMT1 attenuated the effect of MPM in activating the AKT pathway, whereas inhibition of the AKT pathway abrogated the role of MPM in promoting cardiomyocyte proliferation. Collectively, these results indicate that MPM may promote cardiomyocyte proliferation and thus heart growth by interacting with PTPMT1 to activate the AKT pathway. Our findings identify the novel function and regulatory network of MPM and highlight the importance of micropeptides in cardiomyocyte proliferation and heart growth.

2024-12-01·Translational Cancer Research

PTPMT1 inhibition induces apoptosis and growth arrest of human SCLC cells by disrupting mitochondrial metabolism

Article

作者: Liu, Xiang ; Tian, Fang ; Gao, Chuancheng ; Sun, Yang ; Xu, Qinqin ; Xiao, Fengjun ; Sun, Huiyan

BackgroundMany cancer cells exhibit aberrant metabolic reprogramming through abnormal mitochondrial respiration. Protein tyrosine phosphatase mitochondrial 1 (PTPMT1) is a protein tyrosine phosphatase localized to the mitochondria and linked to mitochondrial respiration. However, the expression and role of PTPMT1 in regulating the biological characteristics of small cell lung cancer (SCLC) has not yet been explored. The aim of this study was to evaluate the role of PTPMT1 on SCLC cell survival and mitochondrial function.MethodsSCLC and adjacent normal tissues were obtained from surgery. The expression level of PTPMT1 in the SCLC tissues and cell lines was determined by immunohistochemical staining, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). PTPMT1 knockdown was induced by lentivirus-mediated short-hairpin RNA (shRNA) transduction and PTPMT1 inhibition (alexidine dihydrochloride). The biological characteristics of the cells were measured by cell counting kit 8 (CCK-8), colony formation assay, and cell migration assay. The mitochondrial function of the cells was measured by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining. The H69 cells were treated with alexidine dihydrochloride, after which transcriptome sequencing and an untargeted metabolomic analysis were performed. The transcriptome differentially expressed genes were measured by qRT-PCR.ResultsPTPMT1 was upregulated in the SCLC tissues compared to the adjacent normal tissues. PTPMT1 inhibition by lentiviral shRNA transduction or specific inhibition resulted in significant growth arrest and apoptosis. The transcriptome sequencing analysis revealed that pathways related to the respiration chain and mitochondrial member protein were disrupted. Several mitochondrial metabolism-related genes, such as FGF21, GDF-15, APLN, and MT-DN6, were dysregulated. Further, PTPMT1 inhibition was found to downregulate Glut expression and disturb mitochondrial function.ConclusionsPTPMT1 was shown to play a critical role in the survival and growth of SCLC cells, and may become a potential therapeutic target.

项与 PTPMT1 相关的新闻（医药）

2025-04-07

·今日头条

破解铁死亡密码！西安交大肝癌研究开辟化疗增效新方向

【导读】鉴于 PTPMT1 在线粒体功能和代谢中的重要地位，从药理学角度针对 PTPMT1 进行靶向治疗被认为是一种很有前景的疾病治疗方式。 4月6日，西安交通大学研究团队在期刊《Cell Death&Disease》上发表了研究论文，题为“Pharmacological targeting of the mitochondrial phosphatase PTPMT1 sensitizes hepatocellular carcinoma to ferroptosis”，本研究中，研究人员主要研究了 PTPMT1 在肝细胞癌（HCC）铁死亡中的作用。研究人员分别采用 CRISPR/Cas9 和慢病毒转导方法建立了 PTPMT1 敲除和 PTPMT1 过表达的人肝癌细胞系。在体外和体内评估了 PTPMT1 在调节 HCC 铁死亡中的作用。本研究揭示了 PTPMT1 与半胱氨酸缺乏诱导的铁死亡之间的密切关联，为人类肝细胞癌的化疗策略提供了新的见解。 https://www.nature.com/articles/s41419-025-07581-5#Sec26 研究背景 01 一些研究人员已经证明，PTPMT1 对心磷脂的生物合成至关重要。PTPMT1 缺乏会影响内质网呼吸作用，并导致内质网形态异常。此外，PTPMT1 在胚胎发育过程中不可或缺。近年来，PTPMT1 在代谢调节中的作用也得到了证实。另一项研究还表明，琥珀酸脱氢酶（SDH）是 PTPMT1 的底物，抑制 PTPMT1 可增强 SDH 的过度磷酸化和激活，这表明 PTPMT1 在葡萄糖稳态中具有潜在作用。鉴于 PTPMT1 在线粒体功能和代谢中的重要地位，针对 PTPMT1 的药物靶向治疗已被视为疾病治疗的一种有前景的方式。抑制 PTPMT1 对乳腺癌和肺癌也有显著的治疗作用。因此，PTPMT1 目前被视为癌症化疗的一个新靶点。肝细胞癌（HCC）是最常见的原发性肝癌类型，也是全球范围内发病率和致死率都很高的癌症之一。人类肝细胞癌通常在晚期才被诊断出来，其特点是化疗药物耐药性高，导致化疗效果有限且治疗后容易复发。因此，克服耐药性的有效策略在抗肝细胞癌治疗中至关重要。越来越多的证据表明，铁死亡这种伴随着显著铁积累和脂质过氧化的新细胞死亡类型，在调节癌细胞对治疗的反应中起着关键作用。作为一种克服化疗耐药性的潜在靶点，诱导铁死亡可逆转癌症对化疗药物的耐药性，而了解与铁死亡敏感性调节相关的机制对于促进铁死亡调节剂的临床应用至关重要。药理学抑制 PTPMT1 可使肝细胞癌对半胱氨酸剥夺诱导的铁死亡敏感化 02 AD 作为 PTPMT1 唯一有效的选择性抑制剂，被用于在肝细胞癌（HCC）中对 PTPMT1 进行药理学抑制。研究结果表明，药理学抑制 PTPMT1 可提高 HCC 细胞对埃拉斯汀诱导的铁死亡的敏感性。此外，研究人员还评估了 AD 处理的 HCC 细胞对索拉非尼的反应。同样，药理学抑制 PTPMT1 显著提高了 HCC 细胞和正常肝细胞对索拉非尼诱导的铁死亡的敏感性。然而，与未处理组相比，AD 处理的 HCC 细胞对 RSL3诱导的细胞死亡以及 iFSP1诱导的细胞死亡并未表现出更高的敏感性。这表明药理学抑制 PTPMT1 特异性地增强了 HCC 对半胱氨酸剥夺诱导的铁死亡的敏感性，但对 GPX4 或 FSP1 抑制诱导的铁死亡的敏感性没有增强。药理学抑制 PTPMT1 可使肝细胞癌对铁死亡敏感研究结论 03 总之，本研究主要阐明了 PTPMT1 与肝细胞癌（HCC）中铁死亡之间的联系。研究人员确定，AD 介导的 PTPMT1 药物抑制通过调节不稳定的铁池和线粒体三羧酸循环，增强了 HCC 对半胱氨酸剥夺诱导的铁死亡的敏感性。本研究发现为人类 HCC 的治疗策略提供了有前景的视角。参考资料： https://www.nature.com/articles/s41419-025-07581-5#Sec26 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。责任声明：本稿件如有错误之处，敬请联系转化医学网客服进行修改事宜！微信号：zhuanhuayixue 热门推荐活动点击免费报名 🕓 上海｜2025年6月12-15日 ▶ 第七届上海国际癌症大会暨中国生物工程学会医学生物技术专业委员会年会暨第六届中德双边论坛 🕓 北京｜2025年09月19-20日 ▶ 第六届单细胞技术应用研讨会暨空间组学前沿研讨会点击对应文字查看详情

基因疗法抗体药物偶联物临床研究临床结果