The Antioxidative Role of Chaperone-Mediated Autophagy as a Downstream Regulator of Oxidative Stress in Human Diseases.

Chaperone-mediated autophagy (CMA) plays an important role in regulating a variety of cellular functions by selectively degrading damaged or functional proteins in the cytoplasm. One of the cellular processes in which CMA participates is the oxidative stress response. Oxidative stress regulates CMA activity, while CMA protects cells from oxidative damage by degrading oxidized proteins and preventing the accumulation of excessive reactive oxygen species (ROS). Changes in CMA activity have been found in many human diseases, and oxidative stress is also involved. Therefore, understanding the interaction mechanism of ROS and CMA will provide new targets for disease treatment. In this review, we discuss the role of CMA in combatting oxidative stress during the development of different conditions, such as aging, neurodegeneration, liver diseases, infections, pulmonary disorders, and cancers.

Comparative proteomic profiling reveals a pathogenic role for the O-GlcNAcylated AIMP2-PARP1 complex in aging-related hepatic steatosis in mice.

The prevalence of non-alcoholic fatty liver disease (NAFLD) increases with aging. However, the mechanism of aging-related NAFLD remains unclear. Herein, we constructed an aging-related hepatic steatosis model and analyzed the differentially expressed proteins (DEPs) in livers from young and old mice using liquid chromatography-mass spectrometry. Five hundred and eighty-eight aging-related DEPs and novel pathways were identified. Aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2), the most significantly upregulated protein, promoted poly(ADP-ribose) polymerase 1 (PARP1) activation in aging-related hepatic steatosis. Additionally, mice liver-specific O-GlcNAcase knockout promoted AIMP2 and PARP1 expression. O-GlcNAc transferase (OGT) overexpression and O-GlcNAcase inhibition by genetic or pharmaceutical manipulations increased AIMP2 and PARP1 levels in vitro. Mechanistically, O-GlcNAcylation increased AIMP2 protein stability, leading to its aggregation. Our study reveals O-GlcNAcylated AIMP2 as a novel pathogenic regulator of aging-related hepatic steatosis.