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将细胞线粒体自噬作为人类癌症的一种治疗策略。

Targeting cellular mitophagy as a strategy for human cancers.

作者信息

Dong Yuming, Zhang Xue

机构信息

School of Stomatology, China Medical University, Shenyang, China.

The VIP Department, School and Hospital of Stomatology, China Medical University, Shenyang, China.

出版信息

Front Cell Dev Biol. 2024 Jul 5;12:1431968. doi: 10.3389/fcell.2024.1431968. eCollection 2024.

Abstract

Mitophagy is the cellular process to selectively eliminate dysfunctional mitochondria, governing the number and quality of mitochondria. Dysregulation of mitophagy may lead to the accumulation of damaged mitochondria, which plays an important role in the initiation and development of tumors. Mitophagy includes ubiquitin-dependent pathways mediated by PINK1/Parkin and non-ubiquitin dependent pathways mediated by mitochondrial autophagic receptors including NIX, BNIP3, and FUNDC1. Cellular mitophagy widely participates in multiple cellular process including metabolic reprogramming, anti-tumor immunity, ferroptosis, as well as the interaction between tumor cells and tumor-microenvironment. And cellular mitophagy also regulates tumor proliferation and metastasis, stemness, chemoresistance, resistance to targeted therapy and radiotherapy. In this review, we summarized the underlying molecular mechanisms of mitophagy and discussed the complex role of mitophagy in diverse contexts of tumors, indicating it as a promising target in the mitophagy-related anti-tumor therapy.

摘要

线粒体自噬是一种选择性清除功能失调线粒体的细胞过程,它控制着线粒体的数量和质量。线粒体自噬失调可能导致受损线粒体的积累,这在肿瘤的发生和发展中起着重要作用。线粒体自噬包括由PINK1/帕金介导的泛素依赖性途径和由线粒体自噬受体(包括NIX、BNIP3和FUNDC1)介导的非泛素依赖性途径。细胞线粒体自噬广泛参与多种细胞过程,包括代谢重编程、抗肿瘤免疫、铁死亡以及肿瘤细胞与肿瘤微环境之间的相互作用。此外,细胞线粒体自噬还调节肿瘤的增殖和转移、干性、化疗耐药性、对靶向治疗和放疗的抗性。在本综述中,我们总结了线粒体自噬的潜在分子机制,并讨论了线粒体自噬在不同肿瘤背景下的复杂作用,表明它是线粒体自噬相关抗肿瘤治疗中一个有前景的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/210f/11257920/a90bc9c54a90/fcell-12-1431968-g001.jpg

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