Biological systems, from simple microorganisms to humans, are characterized by time-dependent degenerative processes which lead to reduced fitness, disabilities, severe diseases, and, finally, death. These processes are under genetic control but also influenced by environmental conditions and by stochastic processes. Studying the mechanistic basis of degenerative processes in the filamentous ascomycete Podospora anserina and in other systems demonstrated that mitochondria play a key role in the expression of degenerative phenotypes and unraveled a number of underlying molecular pathways. Reactive oxygen species (ROS) which are mainly, but not exclusively, formed at the mitochondrial respiratory chain are crucial players in this network. While being essential for signaling processes and development, ROS are, at the same time, a potential danger because they lead to molecular damage and degeneration. Fortunately, a number of interacting pathways including ROS scavenging, DNA and protein repair, protein degradation, and mitochondrial fission and fusion are involved in keeping cellular damage low. If these pathways are overwhelmed by extensive damage, programmed cell death is induced. The current knowledge of this hierarchical system of mitochondrial quality control, although still incomplete, appears now to be ready for the development of strategies effective in interventions into those pathways leading to degeneration and loss of performance also in microorganisms used in biotechnology. Very promising interdisciplinary interactions and collaborations involving academic and industrial research teams can be envisioned to arise which bear a great potential, in particular, when system biology approaches are used to understand relevant networks of pathways in a holistic way.