The autophagy receptor p62/SQST-1 promotes proteostasis and longevity in C. elegans by inducing autophagy

Abstract

AbstractAutophagy can degrade cargos with the help of selective autophagy receptors such as p62/SQSTM1, which facilitates the degradation of ubiquitinated cargo. While the process of autophagy has been linked to aging, the impact of selective autophagy in lifespan regulation remains unclear. We have recently shown inCaenorhabditis elegansthat transcript levels of sqst-1/p62increase upon a hormetic heat shock, suggesting a role of SQST-1/p62 in stress response and aging. Here, we find thatsqst-1/p62is required for hormetic benefits of heat shock, including longevity, improved neuronal proteostasis, and autophagy induction. Furthermore, overexpression of SQST-1/p62 is sufficient to induce autophagy in distinct tissues, extend lifespan, and improve the fitness of mutants with defects in proteostasis in an autophagy-dependent manner. Collectively, these findings illustrate that increased expression of a selective autophagy receptor is sufficient to induce autophagy, enhance proteostasis and extend longevity, and demonstrate an important role forsqst-1/p62in proteotoxic stress responses.