DNA-directed RNA polymerase, mitochondrial (POLRMT)

DNA-directed RNA polymerase, mitochondrial (POLRMT) is a nuclear-encoded enzyme responsible for transcribing mitochondrial DNA (mtDNA) into RNA, essential for the expression of mitochondrial-encoded genes involved in oxidative phosphorylation and energy production. It also functions as the primase during mitochondrial DNA replication. POLRMT is distantly related to bacteriophage T7 RNA polymerase and requires interaction with specific transcription initiation factors, such as TFAM and TFB2M in mammals, for promoter recognition, DNA melting, and subsequent initiation of transcription. Dysregulation of POLRMT impairs mitochondrial function, leading to reduced ATP production, increased oxidative stress, and cellular apoptosis, highlighting its importance in diseases involving mitochondrial dysfunction, such as neurodegeneration, cancer, and diabetic retinopathy (where increased expression is linked to pathological angiogenesis). POLRMT is being targeted by novel drug candidates (e.g., IMT1) in preclinical studies, and it is susceptible to inhibition by some antiviral nucleoside analogs, raising concerns for potential off-target mitochondrial toxicity. The enzyme exhibits structural features homologous to phage RNAP but has evolved to accommodate mammalian mitochondrial transcription mechanisms, requiring specific accessory factors.

Other names

POLRMTAPOLMTMTRNAPMTRPOLh-mtRPOLpolymerase (RNA) mitochondrialRNA polymerase mitochondrialCOXPD55

Inhibition of mitochondrial transcription, Inhibition of RNA primer formation, Direct enzyme inhibition via competitive or non-competitive mechanisms (notably by nucleotide analogs)