REVIEW article
Front. Physiol.
Sec. Metabolic Physiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1678186
Stable Isotope-Resolved Metabolomics in Elucidating Mitochondrial Metabolic Reprogramming and Therapeutic Targets
Provisionally accepted
- 1College of Modern Agriculture, Yibin Vocational and Technical College, Yibin, China
- 2Northeastern University, Shenyang, China
- 3The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, China
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Advances in high-resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR) have established stable isotope-resolved metabolomics (SIRM) as a pivotal methodology for elucidating mitochondrial metabolic reprogramming and its connection to therapeutic targets. By utilizing isotopically labeled substrates and integrating metabolic flux analysis (fluxomics) with computational modeling, SIRM enables the dynamic and quantitative tracking of carbon flux distribution and turnover rates within mitochondrial pathways. Recent applications of this precision approach have delineated characteristic patterns of mitochondrial metabolic reprogramming in cancer, neurodegenerative disorders, and metabolic syndrome; identified critical metabolic dependencies and sources of pathogenic metabolites; and elucidated the mechanisms of action for targeted therapeutic agents. Furthermore, stable isotope-resolved analyses facilitate the assessment of therapeutic efficacy and monitoring of treatment resistance, providing quantitative biomarkers for patient stratification in metabolism-targeted therapies. This review summarizes recent advances, technical challenges, and future directions in SIRM for investigating the nexus between mitochondrial metabolic reprogramming and therapeutic targeting, thereby providing a scientific foundation for optimizing metabolic intervention strategies and accelerating their clinical translation.
Keywords: Stable isotope resolved metabolomics, Mitochondrial metabolic reprogramming, Metabolic Flux Analysis, therapeutic targets, Fluxomics
Received: 18 Aug 2025; Accepted: 15 Oct 2025.
Copyright: © 2025 Yang, Wu and Kang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Tingting Kang, kangtt5@mail.sysu.edu.cn
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