Fig. 3

The interactions between NM-mediated autophagy and other biological effects. NMs endocytosed into cells can impaire various organelles including golgi apparatus, endoplasmic reticulum, mitochondria and lysosomes. The damaged organelles are sequestered by primary autophagosomes, which are fused with lysosomes to form autolysosomes, leading to degradation or autophagic flux blockade occur. Autophagy dysfunction will further cause cell inflammation, oxidative stress, apoptosis and pyroptosis. NMs induced LMP can result in cytoplasmic acidification and release of Fe²⁺, which directly relate to autophagic flux blockage and further cell necrosis. The mitophagy dysfunction can lead to caspase 8 activation, which can inhibit the expression of RIPK3, thereby inhibiting necroptosis. NMs cause RNA damage through the deacetylation of autophagy-related proteins and DNA damage through accumulation of chromosome fragments, both activating the autophagy pathway. Impairment of cytoskeleton is mainly manifested by the damage of actin and the decreased expression of histone deacetylase-6, which eventually leads to the disorder of autophagic flux