Iron　is　an　essential　dietary　micronutrient　for　maintaining　physiological　homeostasis.　However,　disruption　of　cerebral　iron　regulation　with　the　accumulation　of　iron　in　different　brain　structures　appears　to　have　a　role　in　the　pathogenesis　of　various　neurodegenerative　disorders.　Studies　have　reported　that　autophagy　induction　could　potentially　mitigate　progression　in　neurodegenerative　diseases　with　iron　deposition,　but　the　relationship　between　autophagy　and　iron　remains　poorly　understood.　Meanwhile,　abnormal　autophagy　in　microglia　is　closely　related　to　the　occurrence　of　neurodegenerative　diseases.　Therefore,　the　effect　of　iron　on　microglia　autophagy　needs　to　be　elaborated.　In　the　present　study,　we　found　that　iron　induces　autophagosome　accumulation　but　inhibits　its　initiation　in　an　Akt-mTOR　pathway　independent　manner.　Meanwhile,　it　caused　autophagy　flux　defects　and　dysfunction　of　lysosomes.　We　also　found　that　iron　overload　reduced　the　expression　of　Rab7,　which　is　an　essential　protein　for　the　fusion　of　autophagosomes　and　lysosomes.　These　results　suggest　that　iron　induces　the　accumulation　of　autophagosome　in　microglia　and　disrupts　the　autophagic　flux　in　late　stage　of　autophagy.　Therefore,　our　work　provides　new　insights　into　the　molecular　mechanisms　of　iron　neurotoxicity.　©　2023　Elsevier　Ltd