The Role of p62 in Aggregopathies

Abstract p62 is an autophagy receptor for ubiquitinated cargos and plays a role in amino acid sensing and the oxidative stress pathway. In response to stress and starvation, it is attracted to autophagy substrates such as protein aggregates, damaged mitochondria, and intracellular bacteria. Turnover via autophagy is responsible for the degradation of p62. Therefore impairment of autophagy is usually accompanied by accumulation of p62, followed by the formation of aggregate structures positive for p62 and ubiquitin. This aggregation occurs due to the nature of both the predilection for self-oligomerization and the ubiquitin-binding capabilities of p62. In this chapter we will discuss the structure and function of p62 in relation to disease conditions characterized by the presence of protein aggregates (aggregopathies). Whether therapeutic targeting of p62 will be beneficial for all aggregopathies remains open for discussion.