Mitochondrial oxidative damage and human diseases

线粒体氧化损伤与人类疾病

• 批准号: MC_UU_00015/3
• 负责人: Michael Murphy
• 金额: $ 422.27万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00015%2F3
• 关键词: Mitochondrial; oxidative; damage; human; diseases

A number of human diseases are associated with increased cell death caused by free radicals. These include degenerative diseases such as Parkinson's disease, Friedreich's ataxia and diabetes. Free radicals are reactive by-products of normal metabolism that damage cell components thereby disrupting normal function and leading to cell death. Mitochondria are the major source of free radicals within cells. These free radicals are formed as mitochondria consume the oxygen we breathe to make energy available to the cell. Mitochondria are also central to determining how cells die, consequently free radical damage to mitochondria is an important cause of cell death. We have developed procedures to target novel molecules to mitochondria. The hope is that these new molecules will enable us to elucidate the mechanisms by which free radicals damage mitochondria and increase cell death in human diseases. Some of these molecules are antioxidants that should block the effects of free radicals. Therefore this approach may also lead to novel therapies to decrease mitochondrial oxidative stress in human diseases such as Alzheimer's Disease and Parkinson's Disease.

许多人类疾病与自由基引起的细胞死亡增加有关。这些包括退行性疾病，如帕金森氏病、弗里德赖希共济失调和糖尿病。自由基是正常代谢的反应性副产物，其破坏细胞组分，从而破坏正常功能并导致细胞死亡。线粒体是细胞内自由基的主要来源。这些自由基是线粒体消耗我们呼吸的氧气来为细胞提供能量时形成的。线粒体也是决定细胞如何死亡的核心，因此线粒体的自由基损伤是细胞死亡的重要原因。我们已经开发出将新分子靶向线粒体的方法。希望这些新分子将使我们能够阐明自由基破坏线粒体和增加人类疾病中细胞死亡的机制。其中一些分子是抗氧化剂，可以阻止自由基的影响。因此，这种方法也可能导致新的疗法，以减少人类疾病，如阿尔茨海默病和帕金森病的线粒体氧化应激。

项目成果

Cardioprotective mechanisms of mitochondria-targeted S-nitrosating agent and adenosine triphosphate-sensitive potassium channel opener are mutually exclusive

线粒体靶向 S-亚硝化剂和三磷酸腺苷敏感钾通道开放剂的心脏保护机制是相互排斥的

• DOI: 10.17863/cam.83770
• 发表时间: 2021
• 作者: Ahmad T

Fine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila.

• DOI: 10.1371/journal.pgen.1009083
• 发表时间: 2020-11
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Bjedov I;Cochemé HM;Foley A;Wieser D;Woodling NS;Castillo-Quan JI;Norvaisas P;Lujan C;Regan JC;Toivonen JM;Murphy MP;Thornton J;Kinghorn KJ;Neufeld TP;Cabreiro F;Partridge L
• 通讯作者: Partridge L

Mitochondrial respiration is reduced in atherosclerosis, promoting necrotic core formation and reducing relative fibrous cap thickness

动脉粥样硬化中线粒体呼吸减少，促进坏死核心形成并减少相对纤维帽厚度

• DOI: 10.17863/cam.22045
• 发表时间: 2017
• 作者: Bennett M

Cardioprotective mechanisms of mitochondria-targeted S-nitrosating agent and adenosine triphosphate-sensitive potassium channel opener are mutually exclusive.

• DOI: 10.1016/j.xjon.2021.07.036
• 发表时间: 2021-12
• 期刊: JTCVS open
• 作者: Ahmad, Thaniyyah;Wang, Jie;Velez, Ana Karen;Suarez-Pierre, Alejandro;Clement, Kathleen C;Dong, Jie;Sebestyen, Krisztian;Canner, Joseph K;Murphy, Michael P;Lawton, Jennifer S
• 通讯作者: Lawton, Jennifer S

Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis

体内选择性线粒体超氧化物生成通过毒物兴奋效应具有心脏保护作用

• DOI: 10.17863/cam.36909
• 发表时间: 2019
• 作者: Antonucci S