LIPT1

更新于：2025-05-07

基本信息

别名

Lipoate biosynthesis protein、Lipoate-protein ligase、Lipoyl ligase

+ [5]

简介

Lipoyl amidotransferase that catalyzes the transfer of lipoyl moieties from lipoyl-protein H of the glycine cleavage system (lipoyl-GCSH) to E2 subunits of the pyruvate dehydrogenase complex (PDCE2) (PubMed:29987032). Unable to catalyze the transfer of octanoyl from octanoyl-GCSH to PDCE2 (PubMed:29987032). In vitro, it is also able to catalyze the transfer of the lipoyl group from lipoyl-AMP to the specific lysine residue of lipoyl domains of lipoate-dependent enzymes but this reaction may not be physiologically relevant (Probable).

关联

项与 LIPT1 相关的药物

ESD0140656

靶点

LIPT1

作用机制

LIPT1 inhibitors

在研机构

Bayer Pharmaceuticals [+1]

原研机构

The Broad Institute, Inc. [+1]

在研适应症

结直肠癌

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 LIPT1 相关的临床结果

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100 项与 LIPT1 相关的转化医学

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0 项与 LIPT1 相关的专利（医药）

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220

项与 LIPT1 相关的文献（医药）

2025-03-14·Science Advances

Lipoylation inhibition enhances radiation control of lung cancer by suppressing homologous recombination DNA damage repair

Article

作者: Vu, Hieu ; Zhang, Yuanyuan ; Davis, Anthony J. ; Timmerman, Robert D. ; DeBerardinis, Ralph J. ; Ni, Min ; Cai, Feng ; Rosales, Tracy ; Chen, Wei-Min ; Minna, John D. ; Cai, Ling ; Shang, Zengfu ; Chiang, Jui-Chung

Lung cancer exhibits altered metabolism, influencing its response to radiation. To investigate the metabolic regulation of radiation response, we conducted a comprehensive, metabolic-wide CRISPR-Cas9 loss-of-function screen using radiation as selection pressure in human non–small cell lung cancer. Lipoylation emerged as a key metabolic target for radiosensitization, with lipoyltransferase 1 (LIPT1) identified as a top hit. LIPT1 covalently conjugates mitochondrial 2-ketoacid dehydrogenases with lipoic acid, facilitating enzymatic functions involved in the tricarboxylic acid cycle. Inhibiting lipoylation, either through genetic LIPT1 knockout or a lipoylation inhibitor (CPI-613), enhanced tumor control by radiation. Mechanistically, lipoylation inhibition increased 2-hydroxyglutarate, leading to H3K9 trimethylation, disrupting TIP60 recruitment and ataxia telangiectasia mutated (ATM)–mediated DNA damage repair signaling, impairing homologous recombination repair. In summary, our findings reveal a critical role of LIPT1 in regulating DNA damage and chromosome stability and may suggest a means to enhance therapeutic outcomes with DNA-damaging agents.

2025-03-01·Molecular Biotechnology

Identification of Key lncRNAs in Gout Under Copper Death and Iron Death Mechanisms: A Study Based on ceRNA Network Analysis and Random Forest Algorithm

Article

作者: Li, Hua-Nan ; Shao, Zi-Chen ; Sun, Wei-Kang ; Huang, Xin ; Hu, Lie-Kui ; Deng, Qin-Qin ; Cheng, Ling

This study focused on identifying potential key lncRNAs associated with gout under the mechanisms of copper death and iron death through ceRNA network analysis and Random Forest (RF) algorithm, which aimed to provide new insights into the molecular mechanisms of gout, and potential molecular targets for future therapeutic strategies of gout. Initially, we conducted an in-depth bioinformatics analysis of gout microarray chips to screen the key cuproptosis-related genes (CRGs) and key ferroptosis-related genes (FRGs). Using these data, we constructed a key ceRNA network for gout. Finally, key lncRNAs associated with gout were identified through the RF algorithm combined with ROC curves, and validated using the Comparative Toxicogenomics Database (CTD). We successfully identified NLRP3, LIPT1, and DBT as key CRGs associated with gout, and G6PD, PRKAA1, LIG3, PHF21A, KLF2, PGRMC1, JUN, PANX2, and AR as key FRGs associated with gout. The key ceRNA network identified four downregulated key lncRNAs (SEPSECS-AS1, LINC01054, REV3L-IT1, and ZNF883) along with three downregulated mRNAs (DBT, AR, and PRKAA1) based on the ceRNA theory. According to CTD validation inference scores and biological functions of target mRNAs, we identified a potential gout-associated lncRNA ZNF883/hsa-miR-539-5p/PRKAA1 regulatory axis. This study identified the key lncRNA ZNF883 in the context of copper death and iron death mechanisms related to gout for the first time through the application of ceRNA network analysis and the RF algorithm, thereby filling a research gap in this field and providing new insights into the molecular mechanisms of gout. We further found that lncRNA ZNF883 might function in gout patients by regulating PRKAA1, the mechanism of which was potentially related to uric acid reabsorption in the proximal renal tubules and inflammation regulation. The proposed lncRNA ZNF883/hsa-miR-539-5p/PRKAA1 regulatory axis might represent a potential RNA regulatory pathway for controlling the progression of gout disease. This discovery offered new molecular targets for the treatment of gout, and had significant implications for future therapeutic strategies in managing the gout.

2025-03-01·Annals of Medicine & Surgery

Comprehensive analysis the role of cuproptosis related genes in abdominal aortic aneurysm

Article

作者: Chen, Zhongqing ; Huang, Zhenhua ; Xiao, Xiaoyong ; Deng, Zhe ; Liang, Chunhua ; Xiao, Xiaohua ; Liu, Dehong

Immune infiltration plays an important role in the course of abdominal aortic aneurysm (AAA) development, and copper death (cuproptosis) is a new type of programmed cell death recently discovered. Currently, there are no studies on the role of cuproptosis regulating immune infiltration in AAA. We extracted a published GEO dataset (GSE57691), with 49 AAA and 10 control transcriptome sequencing samples. Then, we analyzed the difference of cuproptosis related genes (CRGs) expression between AAA and normal groups. LIPT1, FDX1 and CDKN2A were upregulated in AAA samples (P < 0.05). Subsequently, we analyzed the difference of immune infiltrate cells between the AAA and normal samples. Compared to the normal group, Dendritic cells, Mast activated cells, Monocytes, M0 macrophages, neutrophils, Plasma cells, CD4-naive T cells, follicular-helper T cells and Treg cells were upregulated in the AAA group, while M1 and M2 macrophages, CD4-memory T cells and gamma delta T cells were downregulated. AAA samples were then classified into two subtypes according to the expression profiles of CRGs, the immunological characteristics and function had significant differences between subtypes. Furthermore, we mined 20 hub genes by using Weighted Gene Co-expression Network Analysis (WGCNA) to construct a co-expression network. Three drugs were identified that interacting with eight hub genes based on the gene-drug interaction database. We finally verified the mRNA differences of the CRGs in the aorta of AAA and healthy mice in vitro. LIPT1, CDKN2A and FDX1 may play a role in regulating the development of AAA through immune infiltration. Eight NDUF subunits, including NDUFA1, NDUFA4, and NDUFB1, may also play an important role in this process. In addition, Metformin, ME-344 and NV-128 may be therapeutic agents for AAA by regulating the cuproptosis.