Mechanisms of SOD1 regulation by post-translational modifications

SOD1 is commonly known for its ROS scavenging activity, but recent work has uncovered additional roles in modulating metabolism, maintaining redox balance, and regulating transcription. This new paradigm of expanded SOD1 function raises questions regarding the regulation of SOD1 and the cellular partitioning of its biological roles. Despite decades of research on SOD1, much of which focuses on its pathogenic role in amyotrophic lateral sclerosis, relatively little is known about its regulation by post-translational modifications (PTMs). However, over the last decade, advancements in mass spectrometry have led to a boom in PTM discovery across the proteome, which has also revealed new mechanisms of SOD1 regulation by PTMs and an array of SOD1 PTMs with high likelihood of biological function. In this review, we address emerging mechanisms of SOD1 regulation by post-translational modifications, many of which begin to shed light on how the various functions of SOD1 are regulated within the cell.