ArticleNature communications2021
2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness and promotes the selection of wild-type over mutant mitochondrial DNA.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Emerging therapeutic strategies for mitochondrial DNA-related diseases.Cell reports. Medicine · 2026Review
- Mitochondrial DNA replication is regulated by endoplasmic reticulum-mitochondrial contact sites, the mitochondrial calcium uniporter, and manganese.Nucleic acids research · 2026Article
- Glucose metabolic reprogramming in systemic lupus erythematosus and lupus nephritis: theoretical foundations and therapeutic implications.Frontiers in immunology · 2026Review
- Human OPN-derived peptide SV prevents BPD model through interacting with KIF5B to repair mitochondrial damage and inhibit apoptosis.iScience · 2025Article
- Article
- DNA replication stress underpins the vulnerability to oxidative phosphorylation inhibition in colorectal cancer.Cell death & disease · 2025Article
- The synergistic effect of 2-deoxy-D-glucose and cytarabine on mitochondria of stem-like cells derived from KG1-a.Leukemia research reports · 2025Article
- Inhibition of Glycolysis Alleviates Chronic Unpredictable Mild Stress Induced Neuroinflammation and Depression-like Behavior.Brain sciences · 2024Article
- Fit for purpose: Selecting the best mitochondrial DNA for the job.Cell metabolism · 2024Article
- T cell differentiation drives the negative selection of pathogenic mitochondrial DNA variants.Life science alliance · 2023Article
- Antigen receptor stimulation induces purifying selection against pathogenic mitochondrial tRNA mutations.JCI insight · 2023Article
- Transcriptional and metabolic programs promote the expansion of follicular helper T cells in lupus-prone mice.iScience · 2023Article
- Glucose Requirement of Antigen-Specific Autoreactive B Cells and CD4+ T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- A genome on shaky ground: exploring the impact of mitochondrial DNA integrity on Parkinson's disease by highlighting the use of cybrid models.Cellular and molecular life sciences : CMLS · 2022Review
- 2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart.Scientific reports · 2022Article
- AKAP1 contributes to impaired mtDNA replication and mitochondrial dysfunction in podocytes of diabetic kidney disease.International journal of biological sciences · 2022Article
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 4 countries.
Funding
Abstract
Pathological variants of human mitochondrial DNA (mtDNA) typically co-exist with wild-type molecules, but the factors driving the selection of each are not understood. Because mitochondrial fitness does not favour the propagation of functional mtDNAs in disease states, we sought to create conditions where it would be advantageous. Glucose and glutamine consumption are increased in mtDNA dysfunction, and so we targeted the use of both in cells carrying the pathogenic m.3243A>G variant with 2-Deoxy-D-glucose (2DG), or the related 5-thioglucose. Here, we show that both compounds selected wild-type over mutant mtDNA, restoring mtDNA expression and respiration. Mechanistically, 2DG selectively inhibits the replication of mutant mtDNA; and glutamine is the key target metabolite, as its withdrawal, too, suppresses mtDNA synthesis in mutant cells. Additionally, by restricting glucose utilization, 2DG supports functional mtDNAs, as glucose-fuelled respiration is critical for mtDNA replication in control cells, when glucose and glutamine are scarce. Hence, we demonstrate that mitochondrial fitness dictates metabolite preference for mtDNA replication; consequently, interventions that restrict metabolite availability can suppress pathological mtDNAs, by coupling mitochondrial fitness and replication.
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