The human mitochondrial genome contains a second light strand promoter

Mol Cell. 2022 Oct 6;82(19):3646-3660.e9. doi: 10.1016/j.molcel.2022.08.011. Epub 2022 Aug 30.

Abstract

The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism and supply cells with adequate levels of adenosine triphosphate. Central to this process is the idea that replication primers and gene products both arise via transcription from a single light strand promoter (LSP) such that primer formation can influence gene expression, with no consensus as to how this is regulated. Here, we report the discovery of a second light strand promoter (LSP2) in humans, with features characteristic of a bona fide mitochondrial promoter. We propose that the position of LSP2 on the mitochondrial genome allows replication and gene expression to be orchestrated from two distinct sites, which expands our long-held understanding of mitochondrial gene expression in humans.

Keywords: DdCBE; LSP2; POLRMT; light strand promoter; mitochondria; mitochondrial DNA; mitochondrial gene expression; mitochondrial promoter; mtDNA; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • DNA, Mitochondrial / metabolism
  • Genome, Mitochondrial*
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Transcription, Genetic

Substances

  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • Adenosine Triphosphate