Journal Article Review Epublish
PubMed: 39795950 DOI: 10.3390/ijms26010092
The Role of Mitochondrial Solute Carriers SLC25 in Cancer Metabolic Reprogramming: Current Insights and Future Perspectives.
Int J Mol Sci 26(1)
Authors: Amer Ahmed, Giorgia Natalia Iaconisi, Daria Di Molfetta, Vincenzo Coppola, Antonello Caponio, Ansu Singh, Aasia Bibi, Loredana Capobianco, Luigi Palmieri, Vincenza Dolce, Giuseppe Fiermonte
Affiliations
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy.
- Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
- Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University and Arthur G. James Comprehensive Cancer Center, Columbus, OH 43210, USA.
- Department of Translational Biomedicine and Neuroscience, University of Bari, 70125 Bari, Italy.
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.
Abstract
Cancer cells undergo remarkable metabolic changes to meet their high energetic and biosynthetic demands. The Warburg effect is the most well-characterized metabolic alteration, driving cancer cells to catabolize glucose through aerobic glycolysis to promote proliferation. Another prominent metabolic hallmark of cancer cells is their increased reliance on glutamine to replenish tricarboxylic acid (TCA) cycle intermediates essential for ATP production, aspartate and fatty acid synthesis, and maintaining redox homeostasis. In this context, mitochondria, which are primarily used to maintain energy homeostasis and support balanced biosynthesis in normal cells, become central organelles for fulfilling the heightened biosynthetic and energetic demands of proliferating cancer cells. Mitochondrial coordination and metabolite exchange with other cellular compartments are crucial. The human SLC25 mitochondrial carrier family, comprising 53 members, plays a pivotal role in transporting TCA intermediates, amino acids, vitamins, nucleotides, and cofactors across the inner mitochondrial membrane, thereby facilitating this cross-talk. Numerous studies have demonstrated that mitochondrial carriers are altered in cancer cells, actively contributing to tumorigenesis. This review comprehensively discusses the role of SLC25 carriers in cancer pathogenesis and metabolic reprogramming based on current experimental evidence. It also highlights the research gaps that need to be addressed in future studies. Understanding the involvement of these carriers in tumorigenesis may provide valuable novel targets for drug development.
MeSH
Cells, Homeostasis, Neoplasms, Mitochondria, Carcinogenesis