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Stable Isotope-Resolved Metabolomics in Elucidating Mitochondrial Metabolic Reprogramming and Therapeutic Targets.

Stable Isotope-Resolved Metabolomics in Elucidating Mitochondrial Metabolic Reprogramming and Therapeutic Targets.

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Yibin, CN · Author affiliation

Engineering Center of Agricultural Biosafety Assessment and Biotechnology, School of Advanced Agricultural Sciences, Yibin Vocational and Technical College, Yibin, China.
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Beijing, CN · Author affiliation

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
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Dazhou, CN · Author affiliation

Geriatric Department, Dazhou Central Hospital, Dazhou, China.
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Hangzhou, CN · Author affiliation

Institute of Hematology, Zhejiang University, Hangzhou, China.
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Shenyang, CN · Author affiliation

College of Life and Health Science, Northeastern University, Shenyang, China.
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Shenzhen, CN · Author affiliation

Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
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Baotou, CN · Author affiliation

Inner Mongolia Key Laboratory of Life Health and Bioinformatics, School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China.
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MN · Author affiliation · country only

Inner Mongolia Key Laboratory of Life Health and Bioinformatics, School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China.
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Original abstract

Stable isotope-resolved metabolomics (SIRM) has emerged as a pivotal methodology for dissecting mitochondrial metabolic reprogramming and its connection to therapeutic targets. By combining isotopically labeled substrates with metabolic flux analysis (MFA), SIRM enables dynamic, quantitative tracking of carbon flux through mitochondrial pathways. This review focuses on three disease contexts where SIRM has provided transformative insights: cancer, neurodegenerative disorders (Alzheimer's and Parkinson's diseases), and metabolic syndrome (type 2 diabetes and non-alcoholic fatty liver disease). Recent applications have delineated reprogramming signatures, identified metabolic dependencies, and elucidated drug mechanisms. SIRM also facilitates therapeutic monitoring and resistance assessment, offering quantitative biomarkers for patient stratification. We summarize recent advances, technical challenges, AI-powered innovations, and future directions, providing a foundation for optimizing metabolism-targeted therapies.

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