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Reducing mitochondrial fission results in increased life span and fitness of two fungal ageing models

Abstract

Ageing of biological systems is accompanied by alterations in mitochondrial morphology, including a transformation from networks and filaments to punctuate units1. The significance of these alterations with regard to ageing is not known. Here, we demonstrate that the dynamin-related protein 1 (Dnm1p), a mitochondrial fission protein conserved from yeast to humans2, affects ageing in the two model systems we studied, Podospora anserina and Saccharomyces cerevisiae. Deletion of the Dnm1 gene delays the transformation of filamentous to punctuate mitochondria and retards ageing without impairing fitness and fertility typically observed in long-lived mutants. Our data further suggest that reduced mitochondrial fission extends life span by increasing cellular resistance to the induction of apoptosis and links mitochondrial dynamics, apoptosis and life-span control.

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Figure 1: Analysis of mitochondrial morphology in wild-type (WT) P. anserina and PaDnm1 deletion strain (PaDnm1::ble).
Figure 2: Phenotypic comparison between independent wild-type and PaDnm1::ble strains.
Figure 3: Analysis of age-related parameters in wild-type and PaDnm1 deletion strains of P. anserina.
Figure 4: Analysis of mitochondrial morphology, ROS production and membrane potential in young and old wild-type and dnm1Δ S. cerevisiae.
Figure 5: Effect of dnm1 deletion on S. cerevisiae life span and fitness.

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Acknowledgements

T.N. was sponsored by the Swedish Natural Science Research Council and an award from the Göran Gustafsson Foundation for Scientific Research in Molecular Biology. H.D.O. was supported by grants of the Deutsche Forschungsgemeinschaft, Bonn, Germany. Part of the work of H.D.O. and T.N. is supported by the European Commission (Contract 512020, Acronym: MiMage).

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Correspondence to H.D. Osiewacz.

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supplementary figures S1, S2, S3 and S4 (PDF 470 kb)

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Scheckhuber, C., Erjavec, N., Tinazli, A. et al. Reducing mitochondrial fission results in increased life span and fitness of two fungal ageing models. Nat Cell Biol 9, 99–105 (2007). https://doi.org/10.1038/ncb1524

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