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Mitochondrial type II topoisomerase
- Molecular classification
- Enzyme
01
Overview
Mitochondrial type II topoisomerases are enzymes that regulate the topology of mitochondrial DNA (mtDNA) by introducing transient double-stranded breaks, allowing for the passage of another DNA duplex through the break. This activity is essential for processes such as mtDNA replication, transcription, and segregation. In mammals, two nuclear-encoded type II topoisomerases—Top2α (TOP2A) and Top2β (TOP2B)—have been identified in mitochondria. Type II topoisomerase inhibitors used clinically can affect mitochondrial function due to off-target effects on these enzymes. Disruption can lead to impaired energy metabolism or contribute to drug-induced toxicity.
02
Mechanism of action
Double-stranded DNA breaks with strand passage via ATP hydrolysis
03
Biological functions
DNA replicationTranscriptionmtDNA segregationRegulation of DNA topologyDecatenationRelaxation of supercoiled DNA
04
Disease associations
CancerDrug-induced toxicityMitochondrial dysfunctionImpaired energy metabolism
05
Safety considerations
Off-target effects of topoisomerase II inhibitorsImpaired mitochondrial functionDrug-induced cardiotoxicityPotential for disruption of mtDNA maintenance
06
Interacting drugs
Topoisomerase II inhibitors (e.g., etoposide, doxorubicin)
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