Impact of a Disruption of a Pathway Delivering Copper to Mitochondria onPodospora anserinaMetabolism and Life Span

Abstract

A global depletion of cellular copper as the result of a deficiency in high-affinity copper uptake was previously shown to affect the phenotype and life span of the filamentous fungus Podospora anserina. We report here the construction of a strain in which the delivery of copper to complex IV of the mitochondrial respiratory chain is affected. This strain, PaCox17::ble, is a PaCox17-null mutant that does not synthesize the molecular chaperone targeting copper to cytochrome c oxidase subunit II. PaCox17::ble is characterized by a decreased growth rate, a reduction in aerial hyphae formation, reduced female fertility, and a dramatic increase in life span. The mutant respires via a cyanide-resistant alternative pathway, displays superoxide dismutase (SOD) activity profiles significantly differing from those of the wild-type strain and is characterized by a stabilization of the mitochondrial DNA. Collectively, the presented data define individual components of a molecular network effective in life span modulation and copper as an element with a dual effect. As a cofactor of complex IV of the respiratory chain, it is indirectly involved in the generation of reactive oxygen species (ROS) and thereby plays a life span-limiting role. In contrast, Cu/Zn SOD as a ROS-scavenging enzyme lowers molecular damage and thus positively affects life span. Such considerations explain the reported differences in life span of independent mutants and spread more light on the delicate tuning of the molecular network influencing biological ageing.

Unmasking a temperature-dependent effect of theP. anserinai-AAA protease on aging and development

“…One of the bestcharacterized aging models with a clear mitochondrial etiology of aging is Podospora anserina. In this filamentous fungus, various mitochondrial pathways, including mtDNA reorganization, 23 mtDNA repair, 24 respiration, 25 ROS scavenging, 26,27 copper metabolism, 28 mitochondrial dynamics 29 and apoptosis, [30][31][32] have been demonstrated to play a role. Recently, an impact of the protein quality control system on aging has been demonstrated.…”

Suppression of Mitochondrial DNA Instability of Autosomal Dominant Forms of Progressive External Ophthalmoplegia-AssociatedANT1Mutations inPodospora anserina

“…Furthermore, in contrast to the wild-type strain in which oxygen consumption is very sensitive to cyanide, respiration was $50% resistant to cyanide in the two mutants. In P. anserina, resistance to cyanide has previously been reported in several respiratory mutants partially or completely deficient for complexes III or IV and is due to the induction of an alternative oxidase (AOX) (Dufour et al 2000;Stumpferl et al 2004;Sellem et al 2007). Quantitative RT-PCR experiments revealed that the amount of aox transcripts increased $7-to 20-fold in the mutants compared to the wild type (Table 3).…”

Cyclophilin D links programmed cell death and organismal aging in Podospora anserina

“…6a). Another inducer of oxidative stress with a role in aging and lifespan control is the micronutrient copper (Osiewacz & Borghouts, 2000;Stumpferl et al, 2004;Scheckhuber et al, 2009), an essential cofactor of different enzymes (e.g. cytochrome c oxidase, Cu ⁄ Zn superoxide dismutase).…”