Cellular copper homeostasis, mitochondrial DNA instabilities, and lifespancontrol in the filamentous fungus Podospora anserina

In the fungal aging model Podospora anserina, lifespan is controlled by mit ochondrial and nuclear genetic traits. Different nuclear genes are known to affect the integrity of the mitochondrial DNA (mtDNA). One gene of this ty pe is Grisea encoding a copper-modulated transcription factor involved in t he control of cellular copper homeostasis. The characterization of a long-l ived mutant with a loss-of-function mutation in this gene revealed that the last step in the pathway, homologous recombination, leading to the charact eristic age-related mtDNA reorganizations is copper-dependent. In growing p arts 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. (C) 2000 Published by Elsevie r Science Inc.