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Function and regulation of the divisome for mitochondrial fission

Abstract

Mitochondria form dynamic networks in the cell that are balanced by the flux of iterative fusion and fission events of the organelles. It is now appreciated that mitochondrial fission also represents an end-point event in a signalling axis that allows cells to sense and respond to external cues. The fission process is orchestrated by membrane-associated adaptors, influenced by organellar and cytoskeletal interactions and ultimately executed by the dynamin-like GTPase DRP1. Here we invoke the framework of the ‘mitochondrial divisome’, which is conceptually and operationally similar to the bacterial cell-division machinery. We review the functional and regulatory aspects of the mitochondrial divisome and, within this framework, parse the core from the accessory machinery. In so doing, we transition from a phenomenological to a mechanistic understanding of the fission process.

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Fig. 1: Cellular and physiological importance of the mitochondrial divisome.
Fig. 2: Evolution of the divisome.
Fig. 3: Structure and organization of DRP1.
Fig. 4: Regulation of the mitochondrial divisome.

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Acknowledgements

We thank members of the Pucadyil and Ryan laboratories for comments on the manuscript. K.R. thanks the Council for Scientific and Industrial Research for a graduate fellowship. Work in the Pucadyil laboratory is supported by funds from the Department of Science and Technology‐SERB and the Howard Hughes Medical Institute (HHMI). T.J.P. is an International Scholar of the HHMI. M.T.R. acknowledges support from the Australian Research Council and the National Health and Medical Research Council.

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T.J.P. and M.T.R. conceptualized the manuscript. F.K., K.R., T.J.P. and M.T.R. wrote the manuscript.

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Correspondence to Thomas J. Pucadyil or Michael T. Ryan.

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Kraus, F., Roy, K., Pucadyil, T.J. et al. Function and regulation of the divisome for mitochondrial fission. Nature 590, 57–66 (2021). https://doi.org/10.1038/s41586-021-03214-x

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