Silencing mitochondrial gene expression in living cells
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.
Authors
- Angela Boshnakovska (ORCID: https://orcid.org/0009-0008-3572-0223)
- Stefan Jakobs (ORCID: https://orcid.org/0000-0002-8028-3121)
- Julian Bender (ORCID: https://orcid.org/0000-0003-3316-9999)
- Bettina Warscheid (ORCID: https://orcid.org/0000-0001-5096-1975)
- Luis Daniel Cruz‐Zaragoza (ORCID: https://orcid.org/0000-0001-9568-0245)
- Marcel Morgenstern (ORCID: https://orcid.org/0000-0001-6880-4839)
- Silke Oeljeklaus (ORCID: https://orcid.org/0000-0001-8908-4295)
- Laura S. Kremer (ORCID: https://orcid.org/0000-0002-1647-7538)
- Peter Rehling (ORCID: https://orcid.org/0000-0001-5661-5272)
- Anusha Valpadashi (ORCID: https://orcid.org/0009-0006-4329-9876)
- Michael Lidschreiber (ORCID: https://orcid.org/0000-0002-6740-2755)
- Jan-Niklas Dohrke
- Kristine A. Henningfeld (ORCID: https://orcid.org/0009-0004-7275-0094)
- Sven Dennerlein (ORCID: https://orcid.org/0000-0002-8901-0242)
- Drishan Dahal (ORCID: https://orcid.org/0009-0009-7280-2102)
- Aiturgan Zheenbekova (ORCID: https://orcid.org/0000-0001-7574-0829)
- Mehmet Yilmaz (ORCID: https://orcid.org/0000-0002-5548-3308)
- Mirjam Breuer
- Mats Koschel
- Oliver Urbach (ORCID: https://orcid.org/0009-0001-8641-2000)
Institutions
- University of Würzburg (DE)
- Fraunhofer Institute for Translational Medicine and Pharmacology (DE)
- Universitätsmedizin Göttingen (DE)
- Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 (DE)
- Max Planck Institute for Multidisciplinary Sciences (DE)
- University of Göttingen (DE)
Publication Details
- Journal
- Science
- Published
- 2025-05-22
- DOI
- https://doi.org/10.1126/science.adr3498
- Citations
- 8
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 6.45