Miranda Maria, Bonekamp Nina A, Kühl Inge
Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, D-50931, Germany.
Department of Neuroanatomy, Mannheim Center for Translational Neurosciences (MCTN), Medical Faculty Mannheim, Heidelberg University, Mannheim, D-68167, Germany.
Biol Chem. 2022 Mar 31;403(8-9):779-805. doi: 10.1515/hsz-2021-0416. Print 2022 Jul 26.
Mitochondria are central hubs for cellular metabolism, coordinating a variety of metabolic reactions crucial for human health. Mitochondria provide most of the cellular energy via their oxidative phosphorylation (OXPHOS) system, which requires the coordinated expression of genes encoded by both the nuclear (nDNA) and mitochondrial genomes (mtDNA). Transcription of mtDNA is not only essential for the biogenesis of the OXPHOS system, but also generates RNA primers necessary to initiate mtDNA replication. Like the prokaryotic system, mitochondria have no membrane-based compartmentalization to separate the different steps of mtDNA maintenance and expression and depend entirely on nDNA-encoded factors imported into the organelle. Our understanding of mitochondrial transcription in mammalian cells has largely progressed, but the mechanisms regulating mtDNA gene expression are still poorly understood despite their profound importance for human disease. Here, we review mechanisms of mitochondrial gene expression with a focus on the recent findings in the field of mammalian mtDNA transcription and disease phenotypes caused by defects in proteins involved in this process.
线粒体是细胞代谢的核心枢纽，协调着对人类健康至关重要的各种代谢反应。线粒体通过其氧化磷酸化（OXPHOS）系统提供细胞的大部分能量，该系统需要核基因组（nDNA）和线粒体基因组（mtDNA）编码基因的协调表达。mtDNA的转录不仅对OXPHOS系统的生物发生至关重要，还产生启动mtDNA复制所需的RNA引物。与原核系统一样，线粒体没有基于膜的区室化来分隔mtDNA维持和表达的不同步骤，并且完全依赖于导入细胞器的nDNA编码因子。我们对哺乳动物细胞中线粒体转录的理解有了很大进展，但尽管mtDNA基因表达调控机制对人类疾病至关重要，我们对其仍知之甚少。在这里，我们综述线粒体基因表达的机制，重点关注哺乳动物mtDNA转录领域的最新发现以及该过程中涉及的蛋白质缺陷导致的疾病表型。
