Cellular copper homeostasis, mitochondrial DNA instabilities, and lifespan control in the filamentous fungus Podospora anserina.

In the fungal aging model Podospora anserina, lifespan is controlled by mitochondrial and nuclear genetic traits. Different nuclear genes are known to affect the integrity of the mitochondrial DNA (mtDNA). One gene of this type is Grisea encoding a copper-modulated transcription factor involved in the control of cellular copper homeostasis. The characterization of a long-lived mutant with a loss-of-function mutation in this gene revealed that the last step in the pathway, homologous recombination, leading to the characteristic age-related mtDNA reorganizations is copper-dependent. In growing parts of the culture, the stabilization of the mtDNA has an important impact on the biogenesis of functional mitochondria, on their capacity to remodel damaged respiratory chains and on longevity.