Fig. 6

Signaling pathway mediated by ferritinophagy. In condition of starvation or iron depletion in the cell, ferritinophagy identifies nuclear receptor co-activator 4 (NCOA4) as a specific autophagy cargo receptor, binds ferritin and targets it for lysosomal degradation. Ferritin is a major intracellular iron storage protein complex, which includes ferritin light chain (FTL) and ferritin heavy chain 1 (FTH1). NCOA4 is a cargo receptor that recruits ferritin to autophagosome by binding FTH1 and sequesters ferritin complexes into autophagosomes by binding to microtubule-associated protein 1 light chain 3-phosphatidylethanolamine (LC3-PE) with developing double-membrane of autophagosome. As autophagosome fully matured and fusion with the lysosome which releases hydrolase, both NCOA4 and ferritin are degraded in autolysosome, consequently releasing bioavailable iron