The Role of Free Radicals in Autophagy Regulation: Implications for Ageing

Figure 2

Redox modification of autophagy targets. (a) Oxidative-modified targets are better substrates for CMA degradation. Possible explanations for the increased degradation of oxidised substrates by CMA include (i) partial unfolding of substrates facilitating lysosomal translocation; (ii) partial unfolding of substrates exposing hidden KFERQ-like motifs; (iii) generation of a new KFERQ-like motif due to specific oxidation of amino acid residues. (b) The enrichment of oxidised substrates in mitochondrial-derived vesicles (MDVs) points to a mitochondrial quality control mechanism under oxidative stress conditions. (c) Specific redox modification of targets involved in disease. The interaction of oxidised dopamine with α-synuclein (α-SYN) generates dopamine-modified α-SYN (DA-α-SYN), which is poorly degraded by CMA; it instead forms oligomers and aggregates, further blocking the degradation of other CMA substrates.