Clinical Insights into Mitochondrial Neurodevelopmental and Neurodegenerative Disorders: Their Biosignatures from Mass Spectrometry-Based Metabolomics

被引:11
|
作者
Li, Haorong [1 ]
Uittenbogaard, Martine [2 ]
Hao, Ling [1 ]
Chiaramello, Anne [2 ]
机构
[1] George Washington Univ, Dept Chem, Sci & Engn Hall 4000,800 22nd St NW, Washington, DC 20052 USA
[2] George Washington Univ, Sch Med & Hlth Sci, Dept Anat & Cell Biol, 2300 I St NW Ross Hall 111, Washington, DC 20037 USA
关键词
mitochondrial genetics; neurometabolic coupling; mitochondrial neurodevelopmental disorders; secondary mitochondrial neurodegenerative diseases; mass spectrometry; metabolomics; AMYLOID PRECURSOR PROTEIN; DNA COPY NUMBER; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; ALPHA-SYNUCLEIN; TARGETED METABOLOMICS; PARKINSONS-DISEASE; OXIDATIVE STRESS; ABSOLUTE QUANTIFICATION; PATERNAL INHERITANCE;
D O I
10.3390/metabo11040233
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:24
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