title: Oxidized proteins: mechanisms of removal and consequences of accumulation.
abstract: Elevated levels of oxidized proteins are reported in diseased tissue from age-related pathologies such as atherosclerosis, neurodegenerative disorders, and cataract. Unlike the precise mechanisms that exist for the repair of nucleic acids, lipids, and carbohydrates, the primary pathway for the repair of oxidized proteins is complete catabolism to their constitutive amino acids. This process can be inefficient as is evidenced by their accumulation. It is generally considered that damaged proteins are degraded by the proteasome; however, this is only true for mildly oxidized proteins, because substrates must be unfolded to enter the narrow catalytic core. Rather, evidence suggests that moderately or heavily oxidized proteins are endocytosed and enter the endosomal/lysosomal system, indicating co-operation between the proteasomes and the lysosomes. Heavily modified substrates are incompletely degraded and accumulate within the lysosomal compartments resulting in the formation of lipofuscin-like, autofluorescent aggregates. Accumulation eventually results in impaired turnover of large organelles such as proteasomes and mitochondria, lysosomal destablization, leakage of proteases into the cytosol and apoptosis. In this review, we summarize reports published since our last assessments of the field of oxidized protein degradation including a role for modified proteins in the induction of apoptosis.
authors.affiliation: Cell Biology Group, Heart Research Institute, Camperdown, NSW, Australia. dunlopr@hri.org.au
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Dunlop
authors.forename: Ulf T
authors.initials: UT
authors.lastname: Brunk
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Rodgers
mesh_terms: D000375:Aging / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D010084:Oxidation-Reduction; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
chemical_list: D011506:Proteins; D046988:Proteasome Endopeptidase Complex