文章摘要

MICU1及其与相关疾病的作用机制

作者: 1史喜德, 1郭珊珊, 1李飞, 2,3刘峰舟
1 空军军医大学第一附属医院心内科，西安 710032
2 空军军医大学航空航天医学系航空航天临床医学中心，西安 710032
3 空军军医大学第一附属医院空勤科，西安 710032
通讯: 李飞 Email: lifei01@fmmu.edu.cn
刘峰舟 Email: liufengzhou1986@163.com
DOI: 10.3978/j.issn.2095-6959.2022.07.033
基金: 国家自然科学基金(81870284；82100310)；陕西省重点研发计划一般项目(2021SF-146)。

摘要

线粒体钙离子摄入蛋白1(mitochondrial calcium uptake 1，MICU1)是位于线粒体内膜的线粒体钙稳态的重要调节蛋白。MICU1通过设定线粒体钙离子摄入阈值，调控线粒体钙离子单向转运蛋白(mitochondrial calcium uniporter，MCU)复合物功能，调节线粒体通透性转换孔开放，与MCU及其他线粒体钙调控关键分子相互作用，调节MICU1/MCU比值等多重机制调控线粒体钙稳态，进而参与细胞的能量代谢、氧化应激、增殖、凋亡和铁死亡等生理病理功能。越来越多的研究表明MICU1在心血管、肿瘤、神经系统等疾病发生、发展中起重要作用。然而，这一分子的结构和功能仍不完全清楚，MICU1介导的线粒体Ca2+信号在疾病中的确切作用仍需要进一步的研究，这对于下一步的药物研发及临床应用具有十分重要的意义。
关键词： 线粒体钙离子摄入蛋白1；线粒体钙稳态；心血管；肿瘤；神经系统

Mechanism of MICU1 and its related diseases

Authors: 1SHI Xide, 1GUO Shanshan, 1LI Fei, 2,3LIU Fengzhou
1 Department of Cardiology, First Affiliated Hospital, Air Force Medical University, Xi’an 710032, China
2 Aerospace Clinical Medicine Center, Aerospace Medicine School, Air Force Medical University, Xi’an 710032, China
3 Department of Aviation Medicine, First Affiliated Hospital, Air Force Medical University, Xi’an 710032, China

CorrespondingAuthor: LI Fei Email: lifei01@fmmu.edu.cn

DOI: 10.3978/j.issn.2095-6959.2022.07.033

Foundation: This work was supported by the National Natural Science Foundation (81870284; 82100310) and the Shaanxi Provincial Key Research & Development Plan General Project (2021SF-146), China.

Abstract

The mitochondrial calcium uptake 1 (MICU1) is an important regulatory protein of mitochondrial calcium homeostasis located in the inner membrane of mitochondria. MICU1 regulates mitochondrial calcium homeostasis by setting mitochondrial calcium intake threshold modulating the function of mitochondrial calcium uniporter (MCU) complex, controlling the opening of mitochondrial permeability transition pore, interacting with MCU and other mitochondrial calcium regulation key molecules, and regulating MICU1/MCU ratio to maintain mitochondrial calcium homeostasis, and then participates in physiological and pathological functions such as energy metabolism, oxidative stress, proliferation, apoptosis, and ferroptosis. More and more studies have shown that MICU1 plays an important role in the occurrence and development of cardiovascular disease, tumors, and other nervous system diseases. However, the structure and function of this molecule are still not completely clear. Further research is needed to understand the exact role of MICU1 mediated mitochondrial Ca2+ signaling in diseases, which is of great significance for the next drug development and clinical application.

Keywords： mitochondrial calcium uptake protein 1; mitochondrial calcium homeostasis; cardiovascular; neoplasm; nervous system

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