Li Haorong, Uittenbogaard Martine, Hao Ling, Chiaramello Anne
Department of Chemistry, George Washington University, Science and Engineering Hall 4000, 800 22nd St., NW, Washington, DC 20052, USA.
Department of Anatomy and Cell Biology, School of Medicine and Health Sciences, George Washington University, 2300 I Street N.W. Ross Hall 111, Washington, DC 20037, USA.
Metabolites. 2021 Apr 10;11(4):233. doi: 10.3390/metabo11040233.
Mitochondria are dynamic multitask organelles that function as hubs for many metabolic pathways. They produce most ATP via the oxidative phosphorylation pathway, a critical pathway that the brain relies on its energy need associated with its numerous functions, such as synaptic homeostasis and plasticity. Therefore, mitochondrial dysfunction is a prevalent pathological hallmark of many neurodevelopmental and neurodegenerative disorders resulting in altered neurometabolic coupling. With the advent of mass spectrometry (MS) technology, MS-based metabolomics provides an emerging mechanistic understanding of their global and dynamic metabolic signatures. In this review, we discuss the pathogenetic causes of mitochondrial metabolic disorders and the recent MS-based metabolomic advances on their metabolomic remodeling. We conclude by exploring the MS-based metabolomic functional insights into their biosignatures to improve diagnostic platforms, stratify patients, and design novel targeted therapeutic strategies.
线粒体是动态的多任务细胞器，作为许多代谢途径的枢纽发挥作用。它们通过氧化磷酸化途径产生大部分三磷酸腺苷（ATP），这是大脑依赖的关键途径，以满足其与众多功能相关的能量需求，如突触稳态和可塑性。因此，线粒体功能障碍是许多神经发育和神经退行性疾病的普遍病理标志，导致神经代谢偶联改变。随着质谱（MS）技术的出现，基于MS的代谢组学为其整体和动态代谢特征提供了新的机制理解。在这篇综述中，我们讨论了线粒体代谢紊乱的致病原因以及基于MS的代谢组学在其代谢组重塑方面的最新进展。我们通过探索基于MS的代谢组学对其生物特征的功能见解来改进诊断平台、对患者进行分层并设计新的靶向治疗策略来得出结论。
