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DNA topoisomerase I, mitochondrial (Top1mt), is an enzyme localized exclusively to mitochondria in human cells. It plays a critical role in maintaining the topology of mitochondrial DNA (mtDNA) by relieving supercoiling and torsional stress that arise during mtDNA replication and transcription. This function is essential for proper mitochondrial genome maintenance, gene expression, and overall cellular energy metabolism. Altered expression levels of TOP1MT have been observed in various cancers, and loss-of-function mutations can lead to increased oxidative stress, impaired energy metabolism, and heightened sensitivity to additional cellular stresses. Pharmacological inhibition impairs T cell metabolic fitness by inducing mtDNA damage.
Inhibition of DNA topoisomerase I
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