Proteolethargy is a pathogenic mechanism in chronic disease

The pathogenic mechanisms of many diseases are well understood at the molecular level, but there are prevalent diseases associated with pathogenic signaling, such as diabetes and chronic inflammatory disorders, where our understanding is more limited. Here we report that pathogenic signaling suppresses the mobility of a spectrum of proteins that play essential roles in cellular functions known to be dysregulated in these chronic diseases. This behavior was linked to cysteine residues in the affected proteins and signaling-related increases in excess reactive oxygen species. Diverse pathogenic stimuli, including hyperglycemia, dyslipidemia and inflammation, produce similar suppressed protein mobility phenotypes. We propose that suppressed protein mobility may account for various pathogenic features of diverse chronic diseases.