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线粒体丙酮酸载体在神经疾病中的作用

The Role of Mitochondrial Pyruvate Carrier in Neurological Disorders.

作者信息

Liu Yue, Yu Xiying, Jiang Wei

机构信息

Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

出版信息

Mol Neurobiol. 2025 Mar;62(3):2846-2856. doi: 10.1007/s12035-024-04435-7. Epub 2024 Aug 23.

Abstract

The mitochondrial pyruvate carrier (MPC) is a specific protein complex located in the inner mitochondrial membrane. Comprising a heterodimer of two homodimeric membrane proteins, mitochondrial pyruvate carrier 1 and mitochondrial pyruvate carrier 2, MPC connects cytoplasmic metabolism to mitochondrial metabolism by transferring pyruvate from the cytoplasm to the mitochondria. The nervous system requires substantial energy to maintain its function, and the mitochondrial energy supply is closely linked to neurological function. Mitochondrial dysfunction can induce or exacerbate intracerebral pathologies. MPC influences mitochondrial function due to its specific role as a pyruvate transporter. However, recent studies on MPC and mitochondrial dysfunction in neurological disorders have yielded controversial results, and the underlying mechanisms remain unclear. In this brief review, we provide an overview of the structure and function of MPC. We further discuss the potential mechanisms and feasibility of targeting MPC in treating Parkinson's disease, Alzheimer's disease, and cerebral ischemia/hypoxia injury. This review aims to offer insights into MPC as a target for clinical treatment.

摘要

线粒体丙酮酸载体(MPC)是一种位于线粒体内膜的特定蛋白质复合物。MPC由线粒体丙酮酸载体1和线粒体丙酮酸载体2这两种同二聚体膜蛋白组成异二聚体,通过将丙酮酸从细胞质转移到线粒体,将细胞质代谢与线粒体代谢联系起来。神经系统需要大量能量来维持其功能,而线粒体能量供应与神经功能密切相关。线粒体功能障碍可诱发或加剧脑内病变。MPC因其作为丙酮酸转运体的特定作用而影响线粒体功能。然而,最近关于MPC和神经疾病中线粒体功能障碍的研究产生了有争议的结果,其潜在机制仍不清楚。在这篇简短的综述中,我们概述了MPC的结构和功能。我们进一步讨论了靶向MPC治疗帕金森病、阿尔茨海默病和脑缺血/缺氧损伤的潜在机制和可行性。这篇综述旨在为将MPC作为临床治疗靶点提供见解。

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