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MTHFD2 in healthy and cancer cells: Canonical and non-canonical functions
Natalia Pardo-Lorente1, Sara Sdelci2
1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
Abstract:
Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial enzyme of the folate-mediated one-carbon metabolism pathway. MTHFD2 has become a highly attractive therapeutic target due to its consistent upregulation in cancer tissues and its major contribution to tumor progression, although it also performs vital functions in proliferating healthy cells. Here, we review the diversity of canonical and non-canonical functions of this key metabolic enzyme under physiological conditions and in carcinogenesis. We provide an overview of its therapeutic potential and describe its regulatory mechanisms. In addition, we discuss the recently described non-canonical functions of MTHFD2 and the mechanistic basis of its oncogenic function. Finally, we speculate on novel therapeutic approaches that take into account subcellular compartmentalization and outline new research directions that would contribute to a better understanding of the fundamental roles of this metabolic enzyme in health and disease.
Insights
Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme, is upregulated in cancer and drives tumor progression. This review explores MTHFD2
Area of Science:
- Biochemistry and Molecular Biology
- Cancer Metabolism
Background:
- Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial enzyme crucial for one-carbon metabolism.
- MTHFD2 is consistently upregulated in various cancer tissues, implicating it in tumor progression.
- Its vital roles in both cancer and proliferating healthy cells present a complex therapeutic challenge.
Purpose of the Study:
- To review the diverse canonical and non-canonical functions of MTHFD2 in physiological and carcinogenic conditions.
- To provide an overview of MTHFD2's therapeutic potential and regulatory mechanisms.
- To discuss novel therapeutic strategies and future research directions for MTHFD2.
Main Methods:
- Literature review of existing studies on MTHFD2.
- Analysis of MTHFD2's roles in one-carbon metabolism.
- Discussion of MTHFD2's oncogenic functions and regulatory mechanisms.
Main Results:
- MTHFD2 exhibits both canonical and recently described non-canonical functions.
- Its upregulation is linked to tumor progression, but it also has essential roles in healthy proliferating cells.
- Understanding its subcellular compartmentalization is key to developing targeted therapies.
Conclusions:
- MTHFD2 is a significant therapeutic target in oncology due to its role in cancer metabolism.
- Further research into its non-canonical functions and regulatory mechanisms is warranted.
- Novel therapeutic approaches targeting MTHFD2 hold promise for cancer treatment.
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