Interdisciplinary Program in Neuroscience, School of Systems Biology, George Mason University, Fairfax, VA 22030, USA.
School of Systems Biology, George Mason University, Fairfax, VA 22030, USA.
Biomolecules. 2023 Nov 11;13(11):1638. doi: 10.3390/biom13111638.
Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular control. There are over 1000 known proteins that either reside within the mitochondria or are transiently associated with it. These mitochondrial proteins represent a functional subcellular protein network (mtProteome) that is encoded by mitochondrial and nuclear genomes and significantly varies between cell types and conditions. In neurons, the high metabolic demand and differential energy requirements at the synapses are met by specific modifications to the mtProteome, resulting in alterations in the expression and functional properties of the proteins involved in energy production and quality control, including fission and fusion. The composition of mtProteomes also impacts the localization of mitochondria in axons and dendrites with a growing number of neurodegenerative diseases associated with changes in mitochondrial proteins. This review summarizes the findings on the composition and properties of mtProteomes important for mitochondrial energy production, calcium and lipid signaling, and quality control in neural cells. We highlight strategies in mass spectrometry (MS) proteomic analysis of mtProteomes from cultured cells and tissue. The research into mtProteome composition and function provides opportunities in biomarker discovery and drug development for the treatment of metabolic and neurodegenerative disease.
线粒体是古老的内共生双层膜细胞器,通过能量、代谢和细胞控制来支持广泛的真核细胞功能。有超过 1000 种已知的蛋白质存在于线粒体内部或与之短暂相关。这些线粒体蛋白质代表了一个功能上的亚细胞蛋白质网络(mt 蛋白质组),它由线粒体和核基因组编码,并在细胞类型和条件之间有显著的差异。在神经元中,高代谢需求和突触处的差异能量需求通过 mt 蛋白质组的特定修饰来满足,导致参与能量产生和质量控制的蛋白质的表达和功能特性发生改变,包括分裂和融合。mt 蛋白质组的组成也会影响线粒体在轴突和树突中的定位,越来越多的神经退行性疾病与线粒体蛋白质的变化有关。这篇综述总结了与神经元中线粒体能量产生、钙和脂质信号以及质量控制有关的 mt 蛋白质组的组成和特性的研究结果。我们强调了从培养细胞和组织中进行 mt 蛋白质组的质谱(MS)蛋白质组学分析的策略。对 mt 蛋白质组组成和功能的研究为代谢和神经退行性疾病的治疗提供了生物标志物发现和药物开发的机会。