Mitochondrial RNA granules are fluid condensates, positioned by membrane dynamics
Preprint posted on 27 August 2019 https://www.biorxiv.org/content/10.1101/747055v1
Article now published in Nature Cell Biology at http://dx.doi.org/10.1038/s41556-020-00584-8
Understanding mitochondrial RNA granules with an arsenal of advanced microscopy techniques
Selected by Romain F. Laine
Categories: biophysics, cell biology
Context
Mitochondria are a fascinating eukaryotic cellular organelle, mostly known to be the powerhouse of the cell, by providing a large part of the ATP necessary for cellular metabolism. But mitochondria also contain their own DNA (arranged in foci called nucleoids) and gene expression machinery that support their role in respiratory metabolism [1]. The locally synthesised RNA and associated proteins, on the other hand, associate in so-called mitochondrial RNA granules (MRGs) [1,2]. They are thought to have a role in the regulation of mitochondrial gene expression but their structures (how the different parts are assembled) and biophysical properties (how the granules behave and interact with their surrounding) remain poorly understood.
Key findings
Timo Rey and Sofia Zaganelli, respectively from the labs of Suliana Manley (EPFL) and Jean-Claude Martinou (University of Geneva), have put together an incredible set of microscopy studies to understand the role of mitochondrial RNA granules. Their approach consists in applying specifically chosen quantitative microscopy techniques to obtain some of the important biophysical properties of MRGs:
- Fixed cell high-throughput super-resolution microscopy (htSTORM [3]) to obtain a good understanding of the structures of the granules and nucleoids
- Live-cell FRAP analysis to demonstrate the capacity of the granules to exchange materials with other granules and with their surrounding
- Live-cell time-course super-resolution microscopy (SIM) to observe fusion and fission of mitochondria
- Correlative light-electron microscopy (CLEM) and multi-colour immunofluorescence to establish that the granules are connected to the inner membrane of the mitochondrion
- A combination of live-cell imaging, super-resolution (STED) and CLEM to study these granules in a model of impaired mitochondrial fission
—- htSTORM —- —- FRAP —- —- CLEM —-
What I like about the paper
This paper is an amazing demonstration of how a combination of live-cell and fixed cell, conventional and super-resolution, light and electron microscopy can provide a rich and quantitative analysis of a biophysical cellular entity, supporting and generating new understanding about its role. This is also a sobering lesson of humility (your favorite microscopy technique can rarely do it all on its own) as well as a beautiful example of multidisciplinary work.
Also, RNA granules are ubiquitous which highlights that the cell has other ways to partition and control molecular reactions than membrane-based compartmentalisation (organelles), potentially allowing exchange with its surrounding more rapidly. Cellular life is just so resourceful!
Questions for the authors
If the distribution of MRGs is non-random, what kind of processes could allow their segregation and transport? And how would this be regulated? especially in the context of inheritance.
What other properties of the granules could be studied with the current techniques? How about internal dynamic reorganisation of the granules?
Can the findings on mitochondrial RNA granules inform on the biophysical properties of other types of granules?
References
Posted on: 14 October 2019
doi: https://doi.org/10.1242/prelights.14522
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