The human mitochondrial genome contains a second light strand promoter.

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. [Display omitted] • Human mitochondrial DNA (mtDNA) contains an additional light strand promoter (LSP2) • LSP2 contains identical molecular properties to canonical promoters LSP and HSP • Base edits to LSP2 affect mitochondrial gene transcript levels in living cells Mitochondrial DNA replication primers and light strand gene products were both thought to arise via transcription from a single promoter (LSP) in humans for over 40 years. Tan et al. report the discovery of an additional promoter (LSP2) on the human mitochondrial genome. [ABSTRACT FROM AUTHOR]