State Key Laboratory of Bioactive Substrate and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
State Key Laboratory of Bioactive Substrate and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Biochem Pharmacol. 2022 Mar;197:114891. doi: 10.1016/j.bcp.2021.114891. Epub 2021 Dec 27.
Mitochondria are the principal sites of energy metabolism and provide most of the energy needed for normal cellular function. They are dynamic organelles that constantly undergo fission, fusion and mitophagy to maintain their homeostasis and function. However, dysregulated mitochondrial dynamics and mitophagy leads to reduced ATP generation and mutation of their DNA, which ultimately leads to cell death. Increasing evidence has shown that the FUN14 domain-containing protein 1 (FUNDC1), a novel mitophagy receptor, participates in the process of mitochondrial dynamics and mitophagy and plays a critical role in various human diseases. Herein, we review the role of FUNDC1 in mitophagy and mitochondrial dynamics, thus providing a better understanding of the relationship between the two processes. Moreover, we summarize the treatments targeting FUNDC1, and suggest that FUNDC1 may represent a promising therapeutic target for the treatment of several human diseases such as cardiovascular diseases, metabolic syndrome, cancer and chronic obstructive pulmonary disease (COPD).
线粒体是能量代谢的主要场所,为正常细胞功能提供大部分所需的能量。它们是动态的细胞器,不断经历分裂、融合和自噬,以维持其稳态和功能。然而,线粒体动力学和自噬的失调会导致 ATP 生成减少和其 DNA 的突变,最终导致细胞死亡。越来越多的证据表明,FUN14 结构域包含蛋白 1(FUNDC1),一种新型的自噬受体,参与线粒体动力学和自噬过程,并在各种人类疾病中发挥关键作用。本文综述了 FUNDC1 在自噬和线粒体动力学中的作用,从而更好地理解这两个过程之间的关系。此外,我们总结了针对 FUNDC1 的治疗方法,并提出 FUNDC1 可能代表治疗心血管疾病、代谢综合征、癌症和慢性阻塞性肺疾病(COPD)等几种人类疾病的有前途的治疗靶点。