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Review

Mitochondrial Metabolomics in Cancer: Mass Spectrometry-Based Approaches for Metabolic Rewiring Analysis and Therapeutic Discovery

1
School of Pharmacy and Medical Technology, Putian University, Putian 351100, China
2
Fujian Province University, Key Laboratory of Pharmaceutical Analysis and Laboratory Medicine (Putian University), Putian 351100, China
3
Fujian Province University, Key Laboratory of Medical Microecology (Putian University), Putian 351100, China
4
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 100864, China
5
University of Chinese Academy of Sciences, Beijing 100049, China
6
School of Nursing, Putian University, Putian 351100, China
*
Author to whom correspondence should be addressed.
Metabolites 2025, 15(8), 513; https://doi.org/10.3390/metabo15080513 (registering DOI)
Submission received: 7 March 2025 / Revised: 2 July 2025 / Accepted: 28 July 2025 / Published: 31 July 2025
(This article belongs to the Topic Overview of Cancer Metabolism)

Abstract

Mitochondria, pivotal organelles in cellular metabolism and energy production, have emerged as critical players in the pathogenesis of cancer. This review outlines the progress in mitochondrial profiling through mass spectrometry-based metabolomics and its applications in cancer research. We provide unprecedented insights into the mitochondrial metabolic rewiring that fuels tumorigenesis, metastasis, and therapeutic resistance. The purpose of this review is to provide a comprehensive guide for the implementation of mitochondrial metabolomics, integrating advanced methodologies—including isolation, detection, and data integration—with insights into cancer-specific metabolic rewiring. We first summarize current methodologies for mitochondrial sample collection and pretreatment. Furthermore, we then discuss the recent advancements in mass spectrometry-based methodologies that facilitate the detailed profiling of mitochondrial metabolites, unveiling significant metabolic reprogramming associated with tumorigenesis. We emphasize how recent technological advancements have addressed longstanding challenges in the field and explore the role of mitochondrial metabolism-driven cancer development and progression for novel drug discovery and translational research applications in cancer. Collectively, this review delineates emerging opportunities for therapeutic discovery and aims to establish a foundation for future investigations into the therapeutic modulation of mitochondrial pathways in cancer, thereby paving the way for innovative diagnostic and therapeutic approaches targeting mitochondrial pathways.
Keywords: mitochondrial metabolomics; mass spectrometry; mitochondria isolation; targeted metabolomics; untargeted metabolomics mitochondrial metabolomics; mass spectrometry; mitochondria isolation; targeted metabolomics; untargeted metabolomics

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MDPI and ACS Style

Gao, Y.; Xiong, Z.; Wei, X. Mitochondrial Metabolomics in Cancer: Mass Spectrometry-Based Approaches for Metabolic Rewiring Analysis and Therapeutic Discovery. Metabolites 2025, 15, 513. https://doi.org/10.3390/metabo15080513

AMA Style

Gao Y, Xiong Z, Wei X. Mitochondrial Metabolomics in Cancer: Mass Spectrometry-Based Approaches for Metabolic Rewiring Analysis and Therapeutic Discovery. Metabolites. 2025; 15(8):513. https://doi.org/10.3390/metabo15080513

Chicago/Turabian Style

Gao, Yuqing, Zhirou Xiong, and Xinyi Wei. 2025. "Mitochondrial Metabolomics in Cancer: Mass Spectrometry-Based Approaches for Metabolic Rewiring Analysis and Therapeutic Discovery" Metabolites 15, no. 8: 513. https://doi.org/10.3390/metabo15080513

APA Style

Gao, Y., Xiong, Z., & Wei, X. (2025). Mitochondrial Metabolomics in Cancer: Mass Spectrometry-Based Approaches for Metabolic Rewiring Analysis and Therapeutic Discovery. Metabolites, 15(8), 513. https://doi.org/10.3390/metabo15080513

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