Silencing mitochondrial gene expression in living cells

• 成果类型: Article
• 署名作者: Cruz-Zaragoza, Luis Daniel; Dahal, Drishan; Koschel, Mats; Boshnakovska, Angela; Zheenbekova, Aiturgan; Yilmaz, Mehmet; Morgenstern, Marcel; Dohrke, Jan-Niklas; Bender, Julian; Valpadashi, Anusha; Henningfeld, Kristine A.; Oeljeklaus, Silke; Kremer, Laura Sophie; Breuer, Mirjam; Urbach, Oliver; Dennerlein, Sven; Lidschreiber, Michael; Jakobs, Stefan; Warscheid, Bettina; Rehling, Peter
• 署名单位: University of Gottingen; UNIVERSITY GOTTINGEN HOSPITAL; University of Wurzburg; University of Gottingen; UNIVERSITY GOTTINGEN HOSPITAL; University of Gottingen
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11744
• DOI: 10.1126/science.adr3498
• 发表日期: 2025-07-31
• 关键词: dna mutations; r package; Visualization

摘要

Mitochondria fulfill central functions in metabolism and energy supply. They express their own genome, which encodes key subunits of the oxidative phosphorylation system. However, the central mechanisms underlying mitochondrial gene expression remain enigmatic, and a lack of suitable technologies to target mitochondrial protein synthesis in cells has limited experimental access. We silenced the translation of specific mitochondrial mRNAs in living human cells by delivering synthetic peptide-morpholino chimeras. This approach allowed us to perform a comprehensive temporal monitoring of cellular responses. Our study provides insights into mitochondrial translation, its integration into cellular physiology, and provides a strategy to address mitochondrial gene expression in living cells. The approach can potentially be used to analyze mechanisms and pathophysiology of mitochondrial gene expression in a range of cellular model systems.