DNA topoisomerase 1, mitochondrial (TOP1MT)

DNA topoisomerase 1, mitochondrial (TOP1MT) is a nuclear-encoded type IB topoisomerase exclusively localized to mitochondria via its N-terminal mitochondrial targeting sequence.[1][3][5] It relieves supercoiling and torsional tension in mitochondrial DNA (mtDNA) during replication and transcription by transiently cleaving and rejoining one DNA strand, requiring divalent metals like Mg2+ or Ca2+ and optimal activity at alkaline pH (8-8.5).[1][3][5] TOP1MT contributes to mtDNA maintenance, interacts with mitochondrial RNA polymerase POLRMT and mitoribosomal subunits like MRPS22 to support transcription elongation and translation, and shows partial redundancy with TOP3A.[1][4] Encoded by the TOP1MT gene on chromosome 8q24.3 with 14 exons highly homologous to nuclear TOP1, it is expressed highly in mitochondria-rich tissues like heart, skeletal muscle, and brain.[3][7] Knockout leads to dysfunctional mitochondrial respiration, increased ROS, DNA damage, compensatory biogenesis (e.g., elevated TFAM, PGC-1, POLG), and impaired oxidative phosphorylation, with roles in tumor growth via OXPHOS complex assembly.[2][4] It is sensitive to camptothecin, enhancing DNA cleavage.[3]

Other names

top1mtmitochondrial topoisomerase ITop1mtmitochondrial type IB topoisomerase

Inhibits religation of topoisomerase-linked DNA breaks, generates DNA strand breaks