Structure, mechanism, and regulation of mitochondrial DNA transcription initiation

J Biol Chem. 2020 Dec 25;295(52):18406-18425. doi: 10.1074/jbc.REV120.011202. Epub 2020 Oct 30.

Abstract

Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and apoptosis. To accomplish these roles, mitochondria rely on the genetic information in their small genome (mitochondrial DNA) and the nucleus. A growing appreciation for mitochondria's role in a myriad of human diseases, including inherited genetic disorders, degenerative diseases, inflammation, and cancer, has fueled the study of biochemical mechanisms that control mitochondrial function. The mitochondrial transcriptional machinery is different from nuclear machinery. The in vitro re-constituted transcriptional complexes of Saccharomyces cerevisiae (yeast) and humans, aided with high-resolution structures and biochemical characterizations, have provided a deeper understanding of the mechanism and regulation of mitochondrial DNA transcription. In this review, we will discuss recent advances in the structure and mechanism of mitochondrial transcription initiation. We will follow up with recent discoveries and formative findings regarding the regulatory events that control mitochondrial DNA transcription, focusing on those involved in cross-talk between the mitochondria and nucleus.

Keywords: DNA transcription; RNA polymerase; enzyme mechanism; enzyme structure; human mitochondrial RNA polymerase; mitochondria; mitochondrial DNA (mtDNA); mitochondrial DNA transcription; mitochondrial gene regulation; structure-function; transcription; transcription initiation factors; transcription regulation; yeast mitochondrial RNA polymerase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • DNA, Mitochondrial / chemistry*
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Gene Expression Regulation*
  • Humans
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Initiation Site*
  • Transcription, Genetic*

Substances

  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • Transcription Factors

Associated data

  • PDB/1QLN
  • PDB/6YMW
  • PDB/6ERP