In quiescence of fission yeast, autophagy and the proteasome collaborate for mitochondrial maintenance and longevity.

Regulation of proliferation and quiescence in response to intra- or extracellular environmental signals are important for medicine and basic biology. Quiescence is relevant to tumorigenesis and tissue regeneration, and the maintenance of post-mitotic cells is important with regard to a number of senescence-related diseases such as neurodegeneration. We employ fission yeast, Schizosaccharomyces pombe, as a model to study quiescence and longevity as this lower eukaryote has a long chronological life span (over months) in quiescence that is induced by nitrogen starvation. We recently reported that autophagy and the proteasome cooperate in proper mitochondrial maintenance in the quiescent phase. Such cooperativity is not found in proliferating cells. In quiescence, the proteasome is required for normal mitochondrial functions; inactivation of the proteasome results in a large accumulation of reactive oxygen species (ROS), diminished mitochondrial function, and the elevation of proteins and compounds having anti-oxidant activities. Autophagy contributes to preventing the lethal accumulation of ROS by degrading mitochondria, the primary source of ROS. Our results indicate that the degradation of mitochondria by autophagy during proteasome dysfunction is a defense mechanism of quiescent cells against the accumulation of ROS.