To eat, or NOt to eat: S-nitrosylation signaling in autophagy

Abstract

Autophagy is the main catabolic cellular process through which cells adapt their needs (e.g., growth and proliferation) to environmental availability of nutrients (e.g., amino acid and glucose) and growth factors. The rapid activation of the autophagy response essentially depends on protein post-translational modifications (PTMs), which act as molecular switches triggering signaling cascades. Deregulation of autophagy contributes to pathological conditions, such as cancer and neurodegeneration. Therefore, understanding how PTMs affect the occurrence of autophagy is of the highest importance for clinical applications. Besides phosphorylation and ubiquitylation, which represent the best known examples of PTMs, redox-based modifications are also emerging as contributing to the regulation of intracellular signaling. Of note, S-nitrosylation of cysteine residues is a redox PTM and is the principal mechanism of nitric oxide-based signaling. Results emerging in recent years suggest that NO has a role in modulating autophagy. However, the function of S-nitrosylation in autophagy regulation remains still unveiled. By this review, we describe the upstream events regulating autophagy activation focusing on recently published evidence implying a S-nitrosylation-dependent regulation.

Keywords: AMPK; mTOR; GSNOR; cysteine; nitric oxide; post-translational modifications; redox signaling.