Interferon-stimulated gene 15(ISG15)and its associated post-translational modification,ISGylation,have evolved from being a mere antiviral effector to a central regulator of diverse cellular processes[1].Beyond its ca...Interferon-stimulated gene 15(ISG15)and its associated post-translational modification,ISGylation,have evolved from being a mere antiviral effector to a central regulator of diverse cellular processes[1].Beyond its canonical role in immune responses,ISGylation—the covalent attachment of ISG15 to substrates—modulates lysosomal function,autophagy,and redox balance.Recent studies reveal its unexpected involvement in copper metabolism,a pathway critical for both cellular homeostasis and pathogen defense.Copper,while essential as a cofactor for enzymes like cytochrome C oxidase and superoxide dismutase(SOD1),and involved in numerous biological processes,is toxic when excess,triggering cuproptosis—a copper-dependent mitochondrial cell death[2,3].Understanding the interplay between ISG15/ISGylation and copper-related pathways can provide insights into fundamental processes of life.展开更多
基金supported by the Natural Science Foundation of China(grant number 82211530059 to J.X.).
文摘Interferon-stimulated gene 15(ISG15)and its associated post-translational modification,ISGylation,have evolved from being a mere antiviral effector to a central regulator of diverse cellular processes[1].Beyond its canonical role in immune responses,ISGylation—the covalent attachment of ISG15 to substrates—modulates lysosomal function,autophagy,and redox balance.Recent studies reveal its unexpected involvement in copper metabolism,a pathway critical for both cellular homeostasis and pathogen defense.Copper,while essential as a cofactor for enzymes like cytochrome C oxidase and superoxide dismutase(SOD1),and involved in numerous biological processes,is toxic when excess,triggering cuproptosis—a copper-dependent mitochondrial cell death[2,3].Understanding the interplay between ISG15/ISGylation and copper-related pathways can provide insights into fundamental processes of life.
