Mitochondrial Oxidative Stress and Aging in the Filamentous Fungus Podospora anserina

Abstract

In the filamentous fungus Podospora anserina, mitochondrial oxidative stress is a major contributor to aging. Reactive oxygen species (ROS) generated as a result of electron leakage during respiration lead to damage of components of the electron transport chain. In aging wild‐type cultures, damaged proteins cannot be replaced because the mitochondrial genes encoding some of the corresponding subunits gradually become deleted from the mitochondrial DNA (mtDNA). Consequently, these defects result in an increased generation of reactive oxygen species and respiration deficits leading to cell death. Analyses of wild‐type strains and of different long‐lived mutants of P. anserina provide strong evidence that molecular mechanisms controlling aging processes in this fungus are complex and act at different levels. A basic mechanism (e.g., damage by ROS) appears to be overlaid by prominent instabilities of the mtDNA.

Development of oxidative stress tolerance resulted in reduced ability to undergo morphologic transitions and decreased pathogenicity in at-butylhydroperoxide-tolerant mutant ofCandida albicans

“…The origin of peroxide and lipid peroxidation products observable in high concentrations in unstressed C. albicans AF06 cultures (Table 3) has yet to be studied, but the imbalance between cyanide-sensitive respiration and SHAM-sensitive respiration (Table 3) may be indicative of heritable mtDNA damage resulting in increased electron leakage from the electron transport chain (Wei et al, 1998;Osiewacz & Borghouts, 2000;Wei & Lee, 2002;Genova et al, 2004;Doudican et al, 2005). Because elements of the respiratory chain contribute to the initiation and maintenance of lipid peroxide chain reactions, any reduction in cytochrome c-dependent respiration, as seen in the C. albicans AF06 mutant, provides benefits in coping with lipid peroxidation-triggered oxidative stress (Evans et al, 1998).…”

Regulated Forms of Cell Death in Fungi

“…Podospora anserina therefore has been used as a model for studying aging (Rizet, 1953 ). Senescence is associated with cytochrome c oxidase (complex IV) activity of the mitochondrial respiratory chain (Dufour et al, 2000 ; Osiewacz and Borghouts, 2000 ; Lorin et al, 2006 ). Although for many years the mitochondrial accumulation of ROS has been considered the key event underlying biological aging and lifespan in P. anserina , recent data indicates that other signals, including the mitochondrial quality control are also implicated in this process (Osiewacz and Bernhardt, 2013 ).…”

Fungal apoptosis: function, genes and gene function

“…At the microscopic level, the peripheral hyphae show abnormal branching and swelling. There is a correlation between the aging process and accumulation of mutated mtDNA leading to mitochondrial genome instability (Osiewacz & Borghouts, 2000; Albert & Sellem, 2002). Strains selected for increased life span were found to be deficient in cytochrome c oxidase (COX) activity as they carried deletions of the first exon of the COX1 gene.…”