Proteolethargy is a pathogenic mechanism in chronic disease. Academic Article uri icon

Overview

abstract

  • The pathogenic mechanisms of many diseases are well understood at the molecular level, but there are prevalent syndromes associated with pathogenic signaling, such as diabetes and chronic inflammation, 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. The reduced protein mobility, which we call proteolethargy, 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 reduced protein mobility phenotypes. We propose that proteolethargy is an overlooked cellular mechanism that may account for various pathogenic features of diverse chronic diseases.

publication date

  • November 27, 2024

Research

keywords

  • Inflammation
  • Reactive Oxygen Species
  • Signal Transduction

Identity

PubMed Central ID

  • PMC11724756

Scopus Document Identifier

  • 85212617335

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2024.10.051

PubMed ID

  • 39610243

Additional Document Info

volume

  • 188

issue

  • 1