The expression of mitochondrial genes is regulated in response to the metabolic needs of different cell types, but the basic mechanisms underlying this process are still poorly understood. In this Review, we describe how different layers of regulation cooperate to fine tune initiation of both mitochondrial DNA (mtDNA) transcription and replication in human cells. We discuss our current understanding of the molecular mechanisms that drive and regulate transcription initiation from mtDNA promoters, and how the packaging of mtDNA into nucleoids can control the number of mtDNA molecules available for both transcription and replication. Indeed, a unique aspect of the mitochondrial transcription machinery is that it is coupled to mtDNA replication, such that mitochondrial RNA polymerase is additionally required for primer synthesis at mtDNA origins of replication. We discuss how the choice between replication-primer formation and genome-length RNA synthesis is controlled at the main origin of replication (OriH) and how the recent discovery of an additional mitochondrial promoter (LSP2) in humans may change this long-standing model.

线粒体基因的表达受到不同细胞类型代谢需求的调节，但这一过程的基本机制仍知之甚少。在这篇综述中，我们描述了不同层次的调控如何合作来微调人类细胞中线粒体 DNA (mtDNA) 转录和复制的启动。我们讨论了目前对驱动和调节 mtDNA 启动子转录起始的分子机制的理解，以及将 mtDNA 包装到类核中如何控制可用于转录和复制的 mtDNA 分子的数量。事实上，线粒体转录机制的一个独特方面是它与 mtDNA 复制耦合，因此在 mtDNA 复制起点处的引物合成还需要线粒体 RNA 聚合酶。我们讨论了复制引物形成和基因组长度 RNA 合成之间的选择如何在主要复制起点 (OriH) 上进行控制，以及最近在人类中发现的额外线粒体启动子 (LSP2) 如何改变这一长期存在的模型。