A causal link between respiration and senescence in Podospora anserina

Abstract

Senescence, a progressive degenerative process leading to agerelated increase in mortality, is found in most eukaryotes. However, the molecular events underlying aging remain largely unknown. Understanding how longevity is regulated is a fundamental problem. Here we demonstrate that the respiratory function is a key factor that contributes to shortening lifespan of the filamentous fungus Podospora anserina. In this organism, senescence is systematically associated with mitochondrial DNA instabilities. We show that inactivation of the nuclear COX5 gene encoding subunit V of the cytochrome c oxidase complex leads to the exclusive use of the alternative respiratory pathway and to a decrease in production of reactive oxygen species. This inactivation results in a striking increase of longevity associated with stabilization of the mitochondrial chromosome. Moreover, accumulation of several senescence-specific mitochondrial DNA molecules is prevented in this nuclear mutant. These findings provide direct evidence of a causal link between mitochondrial metabolism and longevity in Podospora anserina.

Over‐expression of an S‐adenosylmethionine‐dependent methyltransferase leads to an extended lifespan of Podospora anserina without impairments in vital functions

“…One other interesting outcome of the molecular manipulation reported here is that, in contrast to various long-lived mutants of P. anserina (Schulte et al, 1988;Dufour et al, 2000;Osiewacz, 2002b;Gredilla et al, 2006), in which ROS generation is reduced due to a switch from a cytochrome oxidase dependent to an alternative respiration leading to a reduced production of ATP, extension of lifespan in the PaMth1 over-expressing strain is not accompanied by impairments in growth, pigmentation and fertility. Intervention into pathways in which PaMTH1 plays a protective role thus are effective in increasing the healthy period, the 'health span', in the life time of this fungal aging model.…”

Mutations in Two Zinc-Cluster Proteins Activate Alternative Respiratory and Gluconeogenic Pathways and Restore Senescence in Long-Lived Respiratory Mutants ofPodospora anserina

“…Mutations in genes rse2 and rse3 restore senescence in cox5Tble and cyc1-1 contexts: Inactivation of complex III (cyc1-1) or complex IV (cox5Tble) leads to a spectacular increase in life span associated with several phenotypic defects: alteration in germinating mycelium; poorly colored, thin growing mycelium; reduction of the growth rate; and female sterility (Dufour et al 2000, Sellem et al 2007). To shed light on the parameters responsible for these different characteristics, we isolated suppressor mutations able to improve the phenotype of these mutants.…”

“…The gpd-aox strain contains a transgenic copy of the aox gene under the control of the strong constitutive P.anserina gpd promotor associated with a hygromycin resistance cassette (Lorin et al 2001). The long-lived cox5Tble and cyc1-1 strains have been described in Dufour et al (2000) and in Sellem et al (2007), respectively. The DPaKu70 strain inactivated for the KU70 mammalian ortholog provides an efficient method for producing deletion mutants (El-Khoury et al 2008).…”

“…In this organism, all wild-type cultures exhibit an unavoidable arrest of vegetative growth systematically associated with large rearrangements in the mitochondrial DNA (mtDNA). Inactivation of respiratory complex III (mutant cyc1-1) (Sellem et al 2007) or complex IV (mutant cox5Tble) (Dufour et al 2000) results in an extreme increase of life span (.30-fold) associated with a reduction in reactive oxygen species (ROS) levels and an increased stability of the mtDNA. In Caenorhabditis elegans, a class of mutants (Mit mutants) with disruptions (either genetic or mediated by RNA interference) in genes essential for the mitochondrial electron transport chain (ETC) are also long lived (reviewed in Rea 2005 andRea et al 2007).…”

Root Factors Induce Mitochondrial-Related Gene Expression and Fungal Respiration during the Developmental Switch from Asymbiosis to Presymbiosis in the Arbuscular Mycorrhizal FungusGigaspora rosea

“…In addition to the core pathway, these consist of alternative NADH dehydrogenase and/or alternative oxidase. These alternative paths of electron transfer generate less proton motive force and ATP, but they also generate lower amounts of reactive oxygen species, partly responsible for senescence processes (Dufour et al, 2000). We speculate that germinating spores of AM fungi exhibit a low respiratory activity during asymbiotic growth, perhaps by using alternative electron transports, to minimize C consumption from their own resources like trehalose, glycogen, and lipids and from the incorporation of additional carbon in the form of CO 2 (Bago et al, 1999).…”