Molecular Mechanisms Responsible for Increased Vulnerability of the Ageing Oocyte to Oxidative Damage

Figure 3

Repair and degradation mechanisms of oxidised proteins. (a) Elevated ROS induces a state of OS resulting in the peroxidation of lipids and (b) the generation of lipid aldehyde by-products such as 4-HNE. (c) During OS, native proteins can be oxidised directly by ROS or by secondary by-products of oxidation, such as 4-HNE. There are several pathways for the resolution of oxidised proteins; (d) oxidised protein can be degraded into peptides directly by the proteasomes 20S catalytic core, or (e) can be modified by ubiquitin and polyubiquitinated via K48 to be recognised and degraded by the 26S proteasome in an ATP-dependent manner. Alternatively, the oxidised protein can also be recognised by HSP70s. (f) In the case of revisable oxidation, HSP70s, in combination with cochaperones, mediate protein reduction and refolding back to their native form. (g) Where HSP70 recognition occurs and the oxidative modification is irreversible, such as 4-HNE adduction, the HSP70 and an alternate subset of cochaperones act to facilitate protein degradation via mediating polyubiquitination via K63 (recognised by the autophagy machinery) or K48 (recognised by the 26 proteasome).