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铁螯合剂作为自噬诱导剂:潜在作用与局限性。

Iron chelators as mitophagy agents: Potential and limitations.

机构信息

BIOCEV, First Faculty of Medicine, Charles University, Vestec 252 50, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague 120 00, Czech Republic; Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 1, Prague 28 53, Czech Republic.

BIOCEV, First Faculty of Medicine, Charles University, Vestec 252 50, Czech Republic; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague 120 00, Czech Republic.

出版信息

Biomed Pharmacother. 2024 Oct;179:117407. doi: 10.1016/j.biopha.2024.117407. Epub 2024 Sep 11.

Abstract

Mitochondrial autophagy (mitophagy) is very important process for the maintenance of cellular homeostasis, functionality and survival. Its dysregulation is associated with high risk and progression numerous serious diseases (e.g., oncological, neurodegenerative and cardiovascular ones). Therefore, targeting mitophagy mechanisms is very hot topic in the biological and medicinal research. The interrelationships between the regulation of mitophagy and iron homeostasis are now becoming apparent. In short, mitochondria are central point for the regulation of iron homeostasis, but change in intracellular cheatable iron level can induce/repress mitophagy. In this review, relationships between iron homeostasis and mitophagy are thoroughly discussed and described. Also, therapeutic applicability of mitophagy chelators in the context of individual diseases is comprehensively and critically evaluated.

摘要

线粒体自噬(mitophagy)对于维持细胞内环境稳态、细胞功能和生存至关重要。其功能失调与多种严重疾病(如肿瘤、神经退行性和心血管疾病)的高风险和进展密切相关。因此,靶向线粒体自噬机制是生物学和医学研究中的热门话题。线粒体自噬的调节与铁稳态之间的相互关系现在已经很明显。简而言之,线粒体是铁稳态调节的中心,但细胞内可利用铁水平的变化可以诱导/抑制线粒体自噬。在这篇综述中,深入讨论和描述了铁稳态与线粒体自噬之间的关系。此外,还全面而批判性地评估了线粒体自噬螯合剂在特定疾病背景下的治疗应用。

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