Tan Benedict G, Mutti Christian D, Shi Yonghong, Xie Xie, Zhu Xuefeng, Silva-Pinheiro Pedro, Menger Katja E, Díaz-Maldonado Héctor, Wei Wei, Nicholls Thomas J, Chinnery Patrick F, Minczuk Michal, Falkenberg Maria, Gustafsson Claes M
Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg 405 30, Sweden.
Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
Mol Cell. 2022 Oct 6;82(19):3646-3660.e9. doi: 10.1016/j.molcel.2022.08.011. Epub 2022 Aug 30.
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.
人类线粒体基因组必须及时进行复制和表达，以维持能量代谢并为细胞提供足够水平的三磷酸腺苷。这一过程的核心观点是，复制引物和基因产物均通过从单个轻链启动子（LSP）转录产生，从而使得引物形成能够影响基因表达，但对于其调控方式尚无共识。在此，我们报告在人类中发现了第二个轻链启动子（LSP2），其具有真正线粒体启动子的特征。我们提出，LSP2在线粒体基因组上的位置使得复制和基因表达能够从两个不同位点进行协调，这扩展了我们长期以来对人类线粒体基因表达的理解。
