Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, China.
State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Biomed Pharmacother. 2024 Apr;173:116337. doi: 10.1016/j.biopha.2024.116337. Epub 2024 Feb 28.
In myocardial ischemia/reperfusion injury (MIRI), moderate mitophagy is a protective or adaptive mechanism because of clearing defective mitochondria accumulates during MIRI. However, excessive mitophagy lead to an increase in defective mitochondria and ultimately exacerbate MIRI by causing overproduction or uncontrolled production of mitochondria. Phosphatase and tensin homolog (PTEN)-induced kinase 1 (Pink1), Parkin, FUN14 domain containing 1 (FUNDC1) and B-cell leukemia/lymphoma 2 (BCL-2)/adenovirus E1B19KD interaction protein 3 (BNIP3) are the main mechanistic regulators of mitophagy in MIRI. Pink1 and Parkin are mitochondrial surface proteins involved in the ubiquitin-dependent pathway, while BNIP3 and FUNDC1 are mitochondrial receptor proteins involved in the non-ubiquitin-dependent pathway, which play a crucial role in maintaining mitochondrial homeostasis and mitochondrial quality. These proteins can induce moderate mitophagy or inhibit excessive mitophagy to protect against MIRI but may also trigger excessive mitophagy or insufficient mitophagy, thereby worsening the condition. Understanding the actions of these mitophagy mechanistic proteins may provide valuable insights into the pathological mechanisms underlying MIRI development. Based on the above background, this article reviews the mechanism of mitophagy involved in MIRI through Pink1/Parkin pathway and the receptor mediated pathway led by FUNDC1 and BNIP3, as well as the related drug treatment, aim to provide effective strategies for the prevention and treatment of MIRI.
在心肌缺血/再灌注损伤（MIRI）中，适度的线粒体自噬是一种保护或适应性机制，因为它可以清除 MIRI 期间积累的有缺陷的线粒体。然而，过度的线粒体自噬会导致有缺陷的线粒体增加，并最终通过过度产生或失控产生线粒体而加剧 MIRI。磷酸酶和张力蛋白同源物（PTEN）诱导的激酶 1（Pink1）、Parkin、含 FUN14 结构域的 1 （FUNDC1）和 B 细胞白血病/淋巴瘤 2（BCL-2）/腺病毒 E1B19KD 相互作用蛋白 3（BNIP3）是 MIRI 中线粒体自噬的主要机制调节因子。Pink1 和 Parkin 是参与泛素依赖性途径的线粒体表面蛋白，而 BNIP3 和 FUNDC1 是参与非泛素依赖性途径的线粒体受体蛋白，它们在维持线粒体稳态和线粒体质量方面起着至关重要的作用。这些蛋白质可以诱导适度的线粒体自噬或抑制过度的线粒体自噬，从而预防 MIRI，但也可能引发过度的线粒体自噬或不足的线粒体自噬，从而使病情恶化。了解这些线粒体自噬机制蛋白的作用可能为 MIRI 发展的病理机制提供有价值的见解。基于上述背景，本文通过 Pink1/Parkin 途径和由 FUNDC1 和 BNIP3 介导的受体途径综述了参与 MIRI 的线粒体自噬机制，以及相关的药物治疗，旨在为 MIRI 的预防和治疗提供有效的策略。
