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Increasing organismal healthspan by enhancing mitochondrial protein quality control

Nature Cell Biology volume 11, pages 852–858 (2009)Cite this article

A Corrigendum to this article was published on 02 February 2012

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Abstract

Degradation of damaged proteins by members of the protein quality control system is of fundamental importance in maintaining cellular homeostasis. In mitochondria, organelles which both generate and are targets of reactive oxygen species (ROS), a number of membrane bound and soluble proteases are essential components of this system. Here we describe the regulation of Podospora anserina LON (PaLON) levels, an AAA+ family serine protease localized in the matrix fraction of mitochondria. Constitutive overexpression of PaLon results in transgenic strains of the fungal ageing model P. anserina showing increased ATP-dependent serine protease activity. These strains display lower levels of carbonylated (aconitase) and carboxymethylated proteins, reduced secretion of hydrogen peroxide and a higher resistance against exogenous oxidative stress. Moreover, they are characterized by an extended lifespan without impairment of vital functions such as respiration, growth and fertility. The reported genetic manipulation proved to be a successful intervention in organismal ageing and it led to an increase in the healthy lifespan, the healthspan, of P. anserina.

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Figure 1: Overexpression of PaLon encoding the LON protease of P.anserina.
Figure 2: Analysis of oxidative stress tolerance and the release of hydrogen peroxide by strains overexpressing PaLon.
Figure 3: Analysis of oxidative protein damage and degradation of oxidized proteins in strains overexpressing PaLon.
Figure 4: Phenotypic and molecular comparisons of independent wild-type and PaLon_OEx strains.

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Change history

  • 21 December 2011

    In the version of this letter initially published online and in print, the order of inserts in Fig. 3d had been inverted and the picture in Fig. 4e was not that of a juvenile hypha from the PaLon_Ox1 strain. These errors have been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank R. Lill and B. Friguet for the antibodies used in this study. H.D.O. was supported by a grant from the Deutsche Forschungsgemeinschaft. Part of the work of H.D.O. was supported by the European Commission (FP6-518230; Proteomage).

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Authors and Affiliations

  1. Johann Wolfgang Goethe University, Faculty for Biosciences and Cluster of Excellence Macromolecular Complexes, Institute of Molecular Biosciences, Max-von-Laue-Strasse 9, Frankfurt, 60438, Germany

    Karin Luce & Heinz D. Osiewacz

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Contributions

K.L. and H.D.O. designed the experiments, analysed data and wrote the manuscript; H.D.O. supervised the work and K.L. performed the experiments.

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Correspondence to Heinz D. Osiewacz.

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Luce, K., Osiewacz, H. Increasing organismal healthspan by enhancing mitochondrial protein quality control. Nat Cell Biol 11, 852–858 (2009). https://doi.org/10.1038/ncb1893

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