High-resolution imaging reveals for the first time exactly where mitochondrial proteins are made within the mitochondria in human cells.
By Dr Lyndsey Butterworth
Researchers have adapted a method to visualise where proteins are made within human mitochondria. Their findings improve our understanding of how mitochondrial gene expression is organised. This could lead to better diagnostics and potential treatments for those affected by mitochondrial dysfunction.
A team from the Wellcome Centre for Mitochondrial Research (WCMR) in collaboration with the Bioimaging Unit at Newcastle University have published their work in the scientific journal Proceedings of the National Academy of Sciences (PNAS). They show that mitochondrial protein synthesis mostly occurs at specific compartments within the inner mitochondrial membrane. Interestingly, this is separate to where the protein precursors are found and where the machinery needed to build the proteins is assembled.
Mitochondria possess their own genome. This mitochondrial DNA contains instructions for 13 proteins forming part of the oxidative phosphorylation (OXPHOS) machinery needed to generate cellular energy. Until now, it remained unclear how human mitochondrial protein synthesis is distributed both in terms of the whole cell and within individual mitochondria.
The study made the discoveries using a “click chemistry” labelling technique that adds fluorescent tags to newly synthesised mitochondrial proteins. High resolution imaging, including super resolution microscopy, is then applied to locate where the proteins have been made.
Lead author, Remix-funded PhD student Matt Zorkau, said “The architecture of the mitochondrion is intricately linked to the tasks it performs. Combining fluorescent labelling with super resolution microscopy lets us explore this relationship between structure and function at unprecedented detail. The goal of our work was to uncover the spatial organisation of mitochondrial protein synthesis in human mitochondria. In the future the methodology could be applied to uncover species-specific divergences throughout evolution or improve our understanding of mitochondrial disease mechanisms.”
The technique described in the paper is an exciting addition to the tool set used to explore mitochondrial gene expression. How mitochondrial protein synthesis is spatially organised during development, in different cell types and in relation to the cell cycle are some of the new areas that can now be investigated.
Professor Bob Lightowlers, Deputy Director of the Wellcome Centre for Mitochondrial Research and Professor of Molecular Neuroscience, who is co-corresponding author on the paper along with Professor Zofia Chrzanowska-Lightowlers, said “we are so excited to be able to answer such a fundamental question about mitochondrial biology. The field of mitochondrial research is focusing on inventing new cures for patients with mitochondrial disease. To facilitate this search, we need to expand our understanding of how the mitochondrion works. Matt’s studies have provided another piece in that puzzle.”
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To discuss possibilities of super resolution imaging projects using the Stimulated Depletion Emission (STED) microscope involved in this study, contact the BioImaging Unit at Newcastle University.