Mitophagy Signalling in Health and Disease

健康和疾病中的线粒体自噬信号传导

• 批准号: MC_UU_00018/2
• 负责人: Ian Ganley
• 金额: $ 323.9万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00018%2F2
• 关键词: Mitophagy; Signalling; Health; Disease

The cells of our body are constantly exposed to potentially damaging agents from both external sources, such as the sun's harmful UV rays or pathogenic bacteria, as well as internal sources, including free radicals produced by the cell’s metabolic pathways. A key mechanism that helps us cope with this onslaught is autophagy (which literally means self-eating) whereby damaged and unwanted cellular components, such as mitochondria, are targeted for degradation and recycling. Recent work has indicated that impaired autophagy is linked to many diseases such as cancer and neurodegenerative conditions such as Parkinson’s, therefore any drug that could target this process might be advantageous in treating these diseases. The actual mechanisms of autophagy remain elusive and the aim of my lab is to understand how autophagy is regulated and proceeds at the molecular level. We also aim to unravel how the disruption of autophagic pathways can lead to disease and to exploit this information to develop novel therapeutic strategies.

我们身体的细胞不断暴露于来自外部来源的潜在破坏剂，如太阳的有害紫外线或致病细菌，以及内部来源，包括细胞代谢途径产生的自由基。帮助我们科普这种冲击的一个关键机制是自噬（字面意思是自我吞噬），其中受损和不需要的细胞成分，如线粒体，被降解和回收。最近的研究表明，受损的自噬与许多疾病有关，如癌症和帕金森氏症等神经退行性疾病，因此任何能够靶向这一过程的药物都可能有利于治疗这些疾病。自噬的实际机制仍然难以捉摸，我实验室的目的是了解自噬是如何在分子水平上调节和进行的。我们还旨在揭示自噬途径的破坏如何导致疾病，并利用这些信息来开发新的治疗策略。

项目成果

Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson's disease mouse model.

• DOI: 10.1038/s41467-023-42876-1
• 发表时间: 2023-11-13
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Fang, Tracy-Shi Zhang;Sun, Yu;Pearce, Andrew C.;Eleuteri, Simona;Kemp, Mark;Luckhurst, Christopher A.;Williams, Rachel;Mills, Ross;Almond, Sarah;Burzynski, Laura;Markus, Nora M.;Lelliott, Christopher J.;Karp, Natasha A.;Adams, David J.;Jackson, Stephen P.;Zhao, Jin-Feng;Ganley, Ian G.;Thompson, Paul W.;Balmus, Gabriel;Simon, David K.
• 通讯作者: Simon, David K.

Comment on "mt-Keima detects PINK1-PRKN mitophagy in vivo with greater sensitivity than mito-QC".

• DOI: 10.1080/15548627.2021.1907269
• 发表时间: 2021-12
• 期刊: Autophagy
• 影响因子: 13.3
• 作者: Ganley IG;Whitworth AJ;McWilliams TG
• 通讯作者: McWilliams TG

LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages.

• DOI: 10.15252/embj.201798694
• 发表时间: 2018-06-15
• 期刊: The EMBO journal
• 作者: Härtlova A;Herbst S;Peltier J;Rodgers A;Bilkei-Gorzo O;Fearns A;Dill BD;Lee H;Flynn R;Cowley SA;Davies P;Lewis PA;Ganley IG;Martinez J;Alessi DR;Reith AD;Trost M;Gutierrez MG
• 通讯作者: Gutierrez MG

Global ubiquitylation analysis of mitochondria in primary neurons identifies endogenous Parkin targets following activation of PINK1.

• DOI: 10.1126/sciadv.abj0722
• 发表时间: 2021-11-12
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Antico O;Ordureau A;Stevens M;Singh F;Nirujogi RS;Gierlinski M;Barini E;Rickwood ML;Prescott A;Toth R;Ganley IG;Harper JW;Muqit MMK
• 通讯作者: Muqit MMK

Diversity of mitophagy pathways at a glance.

• DOI: 10.1242/jcs.259748
• 发表时间: 2022-12-01
• 期刊: Journal of cell science
• 影响因子: 4