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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Accession codes
References
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).
Okamoto, K. & Shaw, J. M. Mitochondrial morphology and dynamics in yeast and multicellular eukaryotes. Annu. Rev. Genet. 39, 503–536 (2005).
Osiewacz, H. D. & Scheckhuber, C. Q. Senescence in Podospora anserina. in Molecular Biology of Fungal Development 87–108 (Marcel Dekker, New York, Basel, 2002).
Osiewacz, H. D. Genes, mitochondria and aging in filamentous fungi. Ageing Res. Rev. 28, 1–18 (2002).
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).
Osiewacz, H. D. & Esser, K. The mitochondrial plasmid of Podospora anserina: A mobile intron of a mitochondrial gene. Curr. Genet. 8, 299–305 (1984).
Kück, U., Stahl, U. & Esser, K. Plasmid-like DNA is part of mitochondrial DNA in Podospora anserina. Curr. Genet. 3, 151–156 (1981).
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).
Borghouts, C., Kerschner, S. & Osiewacz, H. D. Copper-dependence of mitochondrial DNA rearrangements in Podospora anserina. Curr. Genet. 37, 268–275 (2000).
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).
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).
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).
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).
Otsuga, D. et al. The dynamin-related GTPase, Dnm1p, controls mitochondrial morphology in yeast. J. Cell Biol. 143, 333–349 (1998).
Bleazard, W. et al. The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nature Cell Biol. 1, 298–304 (1999).
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).
Frank, S. et al. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev. Cell 1, 515–525 (2001).
Sugioka, R., Shimizu, S. & Tsujimoto, Y. Fzo1, a protein involved in mitochondrial fusion, inhibits apoptosis. J. Biol. Chem. 279, 52726–52734 (2004).
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).
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).
Skulachev, V. P. Mitochondrial filaments and clusters as intracellular power-transmitting cables. Trends Biochem. Sci. 26, 23–29 (2001).
Fannjiang, Y. et al. Mitochondrial fission proteins regulate programmed cell death in yeast. Genes Dev. 18, 2785–2797 (2004).
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).
Mair, W., Goymer, P., Pletcher, S. D. & Partridge, L. Demography of dietary restriction and death in Drosophila. Science 301, 1731–1733 (2003).
Hermann, G. J. et al. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p. J. Cell Biol. 143, 359–373 (1998).
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).
Esser,K. Podospora anserina. in Handbook of Genetics (ed. King, R. C.) 531–551 (Plenum Press, New York, 1974).
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).
Munkres, K. D. Histochemical detection of superoxide radicals and hydrogen peroxide by Age-1 mutants of Neurospora. Fungal Genet. Newsl. 37, 24–25 (1990).
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).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Information
supplementary figures S1, S2, S3 and S4 (PDF 470 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ncb1524
This article is cited by
-
The bZIP-type transcription factors NapA and RsmA modulate the volumetric ratio and the relative superoxide ratio of mitochondria in Aspergillus nidulans
Biologia Futura (2023)
-
Antagonistic effects of mitochondrial matrix and intermembrane space proteases on yeast aging
BMC Biology (2022)
-
Increased peroxisome proliferation is associated with early yeast replicative ageing
Current Genetics (2022)
-
Mitochondrial function and nutrient sensing pathways in ageing: enhancing longevity through dietary interventions
Biogerontology (2022)
-
Yeast YPK9 deficiency results in shortened replicative lifespan and sensitivity to hydrogen peroxide
Biogerontology (2021)