Figure 3.

Effects of ROS on various aspects of autophagy. ROS promote autophagy initiation by activating ATM to phosphorylate Chk2 at Ser90/Ser93, which in turn inhibits mTOR. In addition, in the peroxisome, PEX5 is phosphorylated and ubiquitinated in an ATM-dependent manner activated by ROS, promoting autophagy by enhancing SQSTM recognition of the cargo (95). In addition, increased ROS inhibit ATG4-mediated LC3 delipidation and promote autophagic vesicle maturation. Higher levels of ROS lead to ATG4 oxidation and inhibit ATG4 deconjugation of LC3 to allow phagosome expansion and promote autophagic membrane formation. Increased intracellular ROS levels can directly activate Ca²⁺ channels in the lysosomal membrane (MCOLN1/TRPML1), inducing Ca²⁺ release and triggering PPP3/calcineurin-dependent TFEB nuclear translocation to promote autophagy. ROS, reactive oxygen species; ATM, ataxia-telangiectasia mutant; CHK2, cell cycle checkpoint kinase 2; PEX5, peroxisome import receptor; SQSTM1, sequestosome1; ATG, autophagy-related gene; PE, phosphatidylethanolamine; MCOLN1, mucolipin 1;TRPML1, Transient Receptor Potential Cation Channel Subfamily;PPP3, protein phosphatase 3;TFEB, transcription factor EB.