Distinct fission signatures predict mitochondrial degradation or biogenesis

Tatjana Kleele (), Timo Rey, Julius Winter, Sofia Zaganelli, Dora Mahecic, Hélène Perreten Lambert, Francesco Paolo Ruberto, Mohamed Nemir, Timothy Wai, Thierry Pedrazzini and Suliana Manley ()
Additional contact information
Tatjana Kleele: École Polytechnique Fédérale de Lausanne (EPFL)
Timo Rey: École Polytechnique Fédérale de Lausanne (EPFL)
Julius Winter: École Polytechnique Fédérale de Lausanne (EPFL)
Sofia Zaganelli: École Polytechnique Fédérale de Lausanne (EPFL)
Dora Mahecic: École Polytechnique Fédérale de Lausanne (EPFL)
Hélène Perreten Lambert: École Polytechnique Fédérale de Lausanne (EPFL)
Francesco Paolo Ruberto: University of Lausanne Medical School
Mohamed Nemir: University of Lausanne Medical School
Timothy Wai: Institut Pasteur, CNRS UMR 3691
Thierry Pedrazzini: University of Lausanne Medical School
Suliana Manley: École Polytechnique Fédérale de Lausanne (EPFL)

Nature, 2021, vol. 593, issue 7859, 435-439

Abstract: Abstract Mitochondrial fission is a highly regulated process that, when disrupted, can alter metabolism, proliferation and apoptosis1–3. Dysregulation has been linked to neurodegeneration3,4, cardiovascular disease3 and cancer5. Key components of the fission machinery include the endoplasmic reticulum6 and actin7, which initiate constriction before dynamin-related protein 1 (DRP1)8 binds to the outer mitochondrial membrane via adaptor proteins9–11, to drive scission12. In the mitochondrial life cycle, fission enables both biogenesis of new mitochondria and clearance of dysfunctional mitochondria through mitophagy1,13. Current models of fission regulation cannot explain how those dual fates are decided. However, uncovering fate determinants is challenging, as fission is unpredictable, and mitochondrial morphology is heterogeneous, with ultrastructural features that are below the diffraction limit. Here, we used live-cell structured illumination microscopy to capture mitochondrial dynamics. By analysing hundreds of fissions in African green monkey Cos-7 cells and mouse cardiomyocytes, we discovered two functionally and mechanistically distinct types of fission. Division at the periphery enables damaged material to be shed into smaller mitochondria destined for mitophagy, whereas division at the midzone leads to the proliferation of mitochondria. Both types are mediated by DRP1, but endoplasmic reticulum- and actin-mediated pre-constriction and the adaptor MFF govern only midzone fission. Peripheral fission is preceded by lysosomal contact and is regulated by the mitochondrial outer membrane protein FIS1. These distinct molecular mechanisms explain how cells independently regulate fission, leading to distinct mitochondrial fates.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03510-6 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:593:y:2021:i:7859:d:10.1038_s41586-021-03510-6

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03510-6

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().