Regulation of cellular protein quality control networks in a multicellular organism

The long-term health of all metazoan cells is linked to protein quality control, which is achieved by proteostasis, a complex network of molecular interactions that determines the health of the proteome under physiological or stress conditions. Studying the regulation of cellular proteostasis in the context of the whole organism has unraveled multiple layers of cell-nonautonomous regulation, including neuronal regulation, cell-to-cell stress signals and endocrine signaling that affect growth, development and aging. Here, we discuss emerging concepts in cell-nonautonomous regulation of protein quality control networks. The identification of organismal modulators of cellular proteostasis may present novel, yet general targets for misfolding disease intervention.