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Bacterial FtsZ induces mitochondrial fission in human cells

Abstract : Mitochondria are key eukaryotic organelles that evolved from an intracellular bacterium, in a process involving bacterial genome rearrangement and streamlining. As mitochondria cannot form de novo , their biogenesis relies on growth and division. In human cells, mitochondrial division plays an important role in processes as diverse as mtDNA distribution, mitochondrial transport and quality control. Consequently, defects in mitochondrial division have been associated with a wide range of human pathologies. While several protists have retained key components of the bacterial division machinery, none have been detected in human mitochondria, where the dynamin-related protein Drp1, a cytosolic GTPase is recruited to the mitochondrial outer membrane, forming helical oligomers that constrict and divide mitochondria. Here, we created a human codon optimized version of FtsZ, the central component of the bacterial division machinery, and fused it to a mitochondrial targeting sequence. Upon expression in human cells, mt-FtsZ was imported into the mitochondrial matrix, specifically localizing at fission sites prior to Drp1 and significantly increasing mitochondrial fission levels. Our data suggests that human mitochondria have an internal, matrix-localized fission machinery, whose structure is sufficiently conserved as to accommodate bacterial FtsZ. We identified interaction partners of mt-FtsZ, and show that expression of PGAM5, FAM210, SFXN3 and MTCH1 induced mitochondrial fission. Our results thus represent an innovative approach for the discovery of novel critical mitochondrial fission components.
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Preprints, Working Papers, ...
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03093327
Contributor : Fabrizia Stavru <>
Submitted on : Sunday, January 3, 2021 - 8:20:09 PM
Last modification on : Friday, January 22, 2021 - 4:16:02 PM
Long-term archiving on: : Sunday, April 4, 2021 - 6:27:43 PM

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2020.01.24.917146v1.full.pdf
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Anna Spier, Martin Sachse, To Nam Tham, Mariette Matondo, Pascale Cossart, et al.. Bacterial FtsZ induces mitochondrial fission in human cells. 2021. ⟨pasteur-03093327⟩

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