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- O-methyltransferase (1)
- Podospora anserina (1)
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Institute
In previous investigations an impact of cellular copper homeostasis on ageing of the ascomycete Podospora anserina has been demonstrated. Here we provide new data indicating that mitochondria play a major role in this process. Determination of copper in the cytosolic fraction using total reflection X-ray fluorescence spectroscopy analysis and eGfp reporter gene studies indicate an age-related increase of cytosolic copper levels. We show that components of the mitochondrial matrix (i.e. eGFP targeted to mitochondria) become released from the organelle during ageing. Decreasing the accessibility of mitochondrial copper in P. anserina via targeting a copper metallothionein to the mitochondrial matrix was found to result in a switch from a copper-dependent cytochrome-c oxidase to a copper-independent alternative oxidase type of respiration and results in lifespan extension. In addition, we demonstrate that increased copper concentrations in the culture medium lead to the appearance of senescence biomarkers in human diploid fibroblasts (HDFs). Significantly, expression of copper-regulated genes is induced during in vitro ageing in medium devoid of excess copper suggesting that cytosolic copper levels also increase during senescence of HDFs. These data suggest that the identified molecular pathway of age-dependent copper dynamics may not be restricted to P. anserina but may be conserved from lower eukaryotes to humans.
PaMTH1 is an O-methyltransferase catalysing the methylation of vicinal hydroxyl groups of polyphenols. The protein accumulates during ageing of Podospora anserina in both the cytosol and in the mitochondrial matrix. The construction and characterisation of a PaMth1 deletion strain provided additional evidence about the function of the protein in the protection against metal induced oxidative stress. Deletion of PaMth1 was found to lead to a decreased resistance against exogenous oxidative stress and to a shortened lifespan suggesting a role of PaMTH1 as a longevity assurance factor in a new molecular pathway involved in lifespan control. Key words: Podospora anserina, knock-out, reactive oxygen species, flavonoids, ageing, O-methyltransferase