Fig. 3

Iron and copper accumulate in senescent cells. In senescent cells, iron accumulation is due to defective autophagic degradation of ferritin by lysosomes. In addition, in aging cells, FTMT accumulates on the outer membranes of defective mitochondria and promotes mitophagy by specifically interacting with the autophagic cargo receptor NCOA4 coupled to the LC3-II double-membrane phagophore. Furthermore, in senescent cells, reductions in the levels of Atp7a (a copper exporter) block autophagic–lysosomal degradation of copper. Atp7a copper transporter copper-transporting ATPase 1, Ctr1 copper transporter 1, FTMT mitochondrial ferritin, LC3 I cytosolic form of LC3, LC3-II LC3-phosphatidylethanolamine conjugate, mtROS mitochondrial ROS, MVB multivesicular body, NCOA4 nuclear receptor coactivator 4, TFR transferrin receptor