Assessing organismal aging in the filamentous fungus Podospora anserina.

Podospora anserina is an extensively studied model organism to unravel the mechanism of organismal aging. This filamentous fungus is short-lived and accessible to experimentation. Aging and lifespan are controlled by genetic and environmental traits and, in this model, have a strong mitochondrial etiology.

A systems biological analysis links ROS metabolism to mitochondrial protein quality control.

The analyses of previously generated Podospora anserina strains in which the mitochondrial superoxide dismutase, PaSOD3, is increased in abundance, revealed unexpected results, which, at first glance, are contradictory to the 'free radical theory of aging' (FRTA). To re-analyze these results, we performed additional experiments and developed a mathematical model consisting of a set of differential equations describing the time course of various ROS (reactive oxygen species), components of the cellular antioxidant system (PaSOD3 and mitochondrial peroxiredoxin, PaPRX1), and PaCLPP, a mitochondrial matrix protease involved in protein quality control. Incorporating these components we could identify a positive feed-back loop and demonstrate that the role of superoxide as the primary ROS responsible for age-related molecular damage is more complicated than originally stated by the FRTA.

PaCATB, a secreted catalase protecting Podospora anserina against exogenous oxidative stress.

A differential mass spectrometry analysis of secreted proteins from juvenile and senescent Podospora anserina cultures revealed age-related differences in protein profiles. Among other proteins with decreased abundance in the secretome of senescent cultures a catalase, termed PaCATB, was identified. Genetic modulation of the abundance of PaCATB identified differential effects on the phenotype of the corresponding strains.

Increasing mitochondrial superoxide dismutase abundance leads to impairments in protein quality control and ROS scavenging systems and to lifespan shortening.

The fungal aging model Podospora anserina contains three superoxide dismutases (SODs) in different cellular compartments. While PaSOD1 represents the Cu/Zn isoform located in the cytoplasm and in the mitochondrial inter-membrane space, PaSOD2 localizes to the perinuclear ER. PaSOD3, a protein with a manganese binding domain and a mitochondrial targeting sequence (MTS) is the mitochondrial SOD.