Metabolism and aging in the filamentous fungus Podospora anserina

In Podospora anserina, lifespan is under the control of environmental and genetic factors. Both suggest an important impact of metabolism on lifespan and aging. Environmental changes of temperature, of the carbon source in the growth medium, or the addition of specific inhibitors to the growth medium are some of the investigated factors. Genetic approaches underscore the significance of metabolism. In particular, the mitochondrial electron transport plays a major role. As a by-product of a cytochrome oxidase (COX) dependent energy transduction, reactive oxygen species (ROS) are generated and lead to damage of cellular biomolecules. Damaged mitochondria, compromised at complex IV (COX) of the respiratory chain, signal to the nucleus and induce a nuclear gene, PaAox, encoding an alternative oxidase (AOX). This pathway resembles the retrograde response that, at least in yeast, is induced by dysfunctional mitochondria. ROS generation is lowered when electrons are transferred via an alternative pathway utilizing the AOX. As a consequence, lifespan of the corresponding strains is increased. Cellular copper levels were found to play a significant role not only in the generation of ROS but also have an impact on the cytoplasmic and the mitochondrial superoxide dismutase (SOD). In addition, copper is involved in the control of mitochondrial DNA rearrangements and affects the ability of the system to remodel damaged mitochondria. All these different components and pathways are part of the complex molecular network involved in lifespan control of this aging model. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.