What is it about?

The cell is highly organized. Many cellular compartments are demarcated by membranes, but there are many membraneless cellular structures that behave as liquid-like droplets. Collectively, they are called biomolecular condensates and form by separation of molecules that do not like to mix, akin to the behavior of wax and water in a lava lamp. Little is known about how biomolecular condensates support the various functions of the cell. We concentrated the biomolecular machinery that expresses genes in mitochondria into a membraneless droplet, enabling us to study how the structure and function of a condensate are interrelated. We observe that, on their own, the components of the mitochondrial gene expression machinery – DNA and proteins – readily come together to form droplets, albeit not very dynamic ones. Once we trigger the gene expression process, we start to see ring-like structures appear, particularly vesicles, which tend to have slower rates of RNA production than if all of the components were freely in solution. A conundrum was that these vesicular structures are not normally inside of mitochondria in living cells. Our computer simulations suggest that the reason for this difference is that the cell relies on biophysical mechanisms to remove newly made RNA from its DNA- and protein-rich condensates and thus prevent vesicle formation.

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Why is it important?

This study takes advantage of the simplicity of mitochondrial biology as only a few biomolecules are needed for gene expression. The small number of biological players makes for a tractable system to study gene expression inside of a condensate and to model it exactly. From this work, it becomes clear that the structure of a condensate is closely related to the activities occurring within it. Our findings also challenge previous assumptions, such as that reaction rates must always go up in concentrated condensates. This system thus allows us to identify fundamental biophysical mechanisms, which will pave the way for engineering condensates elsewhere in the cell.

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This page is a summary of: Mesoscale structure–function relationships in mitochondrial transcriptional condensates, Proceedings of the National Academy of Sciences, October 2022, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2207303119.
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