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


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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  1. Bossy-Wetzel, E., Barsoum, M. J., Godzik, A., Schwarzenbacher, R. & Lipton, S. A. Mitochondrial fission in apoptosis, neurodegeneration and aging. Curr. Opin. Cell Biol. 15, 706–716 (2003).

    Article  CAS  Google Scholar 

  2. Okamoto, K. & Shaw, J. M. Mitochondrial morphology and dynamics in yeast and multicellular eukaryotes. Annu. Rev. Genet. 39, 503–536 (2005).

    Article  CAS  Google Scholar 

  3. Osiewacz, H. D. & Scheckhuber, C. Q. Senescence in Podospora anserina. in Molecular Biology of Fungal Development 87–108 (Marcel Dekker, New York, Basel, 2002).

    Chapter  Google Scholar 

  4. Osiewacz, H. D. Genes, mitochondria and aging in filamentous fungi. Ageing Res. Rev. 28, 1–18 (2002).

    Google Scholar 

  5. Belcour, L., Begel, O., Mosse, M. O. & Vierny-Jamet, C. Mitochondrial DNA amplification in senescent cultures of Podospora anserina: variability between the retained, amplified sequences. Curr. Genet. 3, 13–21 (1981).

    Article  CAS  Google Scholar 

  6. Osiewacz, H. D. & Esser, K. The mitochondrial plasmid of Podospora anserina: A mobile intron of a mitochondrial gene. Curr. Genet. 8, 299–305 (1984).

    Article  CAS  Google Scholar 

  7. Kück, U., Stahl, U. & Esser, K. Plasmid-like DNA is part of mitochondrial DNA in Podospora anserina. Curr. Genet. 3, 151–156 (1981).

    Article  Google Scholar 

  8. Prillinger, H. & Esser, K. The phenoloxidases of the ascomycete Podospora anserina. XIII. Action and interaction of genes controlling the formation of laccase. Mol. Gen. Genet. 156, 333–345 (1977).

    Article  CAS  Google Scholar 

  9. Borghouts, C., Kerschner, S. & Osiewacz, H. D. Copper-dependence of mitochondrial DNA rearrangements in Podospora anserina. Curr. Genet. 37, 268–275 (2000).

    Article  CAS  Google Scholar 

  10. Borghouts, C., Werner, A., Elthon, T. & Osiewacz, H. D. Copper-modulated gene expression and senescence in the filamentous fungus Podospora anserina. Mol. Cell Biol. 21, 390–399 (2001).

    Article  CAS  Google Scholar 

  11. Borghouts, C., Scheckhuber, C. Q., Werner, A. & Osiewacz, H. D. Respiration, copper availability and SOD activity in P. anserina strains with different lifespan. Biogerontology 3, 143–153 (2002).

    Article  CAS  Google Scholar 

  12. Borghouts, C., Scheckhuber, C. Q., Stephan, O. & Osiewacz, H. D. Copper homeostasis and aging in the fungal model system Podospora anserina: differential expression of PaCtr3 encoding a copper transporter. Int. J. Biochem. Cell. Biol. 34, 1355–1371 (2002).

    Article  CAS  Google Scholar 

  13. Gredilla, R., Grief, J. & Osiewacz, H. D. Mitochondrial free radical generation and lifespan control in the fungal aging model Podospora anserina. Exp. Gerontol. 41, 439–447 (2006).

    Article  CAS  Google Scholar 

  14. Otsuga, D. et al. The dynamin-related GTPase, Dnm1p, controls mitochondrial morphology in yeast. J. Cell Biol. 143, 333–349 (1998).

    Article  CAS  Google Scholar 

  15. Bleazard, W. et al. The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nature Cell Biol. 1, 298–304 (1999).

    Article  CAS  Google Scholar 

  16. Hamann, A., Krause, K., Werner, A. & Osiewacz, H. D. A two-step protocol for efficient deletion of genes in the filamentous ascomycete Podospora anserina. Curr. Genet. 48, 270–245 (2005).

    Article  CAS  Google Scholar 

  17. Frank, S. et al. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev. Cell 1, 515–525 (2001).

    Article  CAS  Google Scholar 

  18. Sugioka, R., Shimizu, S. & Tsujimoto, Y. Fzo1, a protein involved in mitochondrial fusion, inhibits apoptosis. J. Biol. Chem. 279, 52726–52734 (2004).

    Article  CAS  Google Scholar 

  19. Lee, Y. J., Jeong, S. Y., Karbowski, M., Smith, C. L. & Youle, R. J. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. Mol. Biol. Cell 15, 5001–5011 (2004).

    Article  CAS  Google Scholar 

  20. Szabadkai, G. et al. Drp-1-dependent division of the mitochondrial network blocks intraorganellar Ca2+ waves and protects against Ca2+-mediated apoptosis. Mol. Cell 16, 59–68 (2004).

    Article  CAS  Google Scholar 

  21. Skulachev, V. P. Mitochondrial filaments and clusters as intracellular power-transmitting cables. Trends Biochem. Sci. 26, 23–29 (2001).

    Article  CAS  Google Scholar 

  22. Fannjiang, Y. et al. Mitochondrial fission proteins regulate programmed cell death in yeast. Genes Dev. 18, 2785–2797 (2004).

    Article  CAS  Google Scholar 

  23. Mozdy, A. D., McCaffery, J. M. & Shaw, J. M. Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J. Cell Biol. 151, 367–380 (2000).

    Article  CAS  Google Scholar 

  24. Mair, W., Goymer, P., Pletcher, S. D. & Partridge, L. Demography of dietary restriction and death in Drosophila. Science 301, 1731–1733 (2003).

    Article  CAS  Google Scholar 

  25. Hermann, G. J. et al. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p. J. Cell Biol. 143, 359–373 (1998).

    Article  CAS  Google Scholar 

  26. Rapaport, D., Brunner, M., Neupert, W. & Westermann, B. Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae. J. Biol. Chem. 273, 20150–20155 (1998).

    Article  CAS  Google Scholar 

  27. Esser,K. Podospora anserina. in Handbook of Genetics (ed. King, R. C.) 531–551 (Plenum Press, New York, 1974).

    Google Scholar 

  28. Chaveroche, M. K., Ghigo, J. M. & d'Enfert, C. A. A rapid method for efficient gene replacement in the filamentous fungus Aspergillus nidulans. Nucleic Acids Res. 28, E97 (2000).

    Article  CAS  Google Scholar 

  29. Munkres, K. D. Histochemical detection of superoxide radicals and hydrogen peroxide by Age-1 mutants of Neurospora. Fungal Genet. Newsl. 37, 24–25 (1990).

    Google Scholar 

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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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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).

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