Mitochondrial group II introns, cytochrome c oxidase, and senescence in Podospora anserina

Podospora anserina is a filamentous fungus with a limited life span. It exp resses a degenerative syndrome called senescence, which is always associate d with the accumulation of circular molecules (senDNAs) containing specific regions of the mitochondrial chromosome. A mobile group II intron (alpha) has been thought to play a prominent role in this syndrome. Intron alpha is the first intron of the cytochrome c oxidase subunit I gene (COX1). Mitoch ondrial mutants that escape the senescence process are missing this intron, as well as the first exon of the COX1 gene. We describe here the first mut ant of P. anserina that has the or sequence precisely deleted and whose cyt ochrome c oxidase activity is identical to that of wild-type cells. The int egration site of the intron is slightly modified, and this change prevents efficient homing of intron alpha. We show here that this mutant displays a senescence syndrome similar to that of the wild type and that its life span is increased about twofold. The introduction of a related group II intron into the mitochondrial genome of the mutant does not restore the wild-type life span. These data clearly demonstrate that intron or is not the specifi c senescence factor but rather an accelerator or amplifier of the senescenc e process. They emphasize the role that intron or plays in the instability of the mitochondrial chromosome and the link between this instability and l ongevity. Our results strongly support the idea that in Podospora, "immorta lity" can be acquired not by the absence of intron alpha but rather by the lack of active cytochrome c oxidase.