title: TLR4-mediated autophagy in macrophages is a p62-dependent type of selective autophagy of aggresome-like induced structures (ALIS).
abstract: Autophagy plays an evolutionarily conserved role in host defense against pathogens. Autophagic protection mechanisms against microbes range from regulating immune signaling responses to directly targeting the pathogens for lysosomal degradation. Toll-like receptors (TLRs) that detect conserved molecular features shared by pathogens regulate several innate immune responses including autophagy. Our recent study demonstrates that autophagy reported in response to TLR4-stimulation in macrophages is selective autophagy of aggresome-like induced structures (ALIS), and p62 (also known as SQSTM1) plays an essential role in this process. Treatment of macrophages with either Escherichia coli or lipopolysaccharide (LPS) results in the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), leading to an increase in the levels of p62 mRNA and protein, assembly of ALIS and their autophagic degradation. This study revealed a signaling role for p62, distinct from its known function as a bacterial-targeting factor, which might be critical for cellular stress response during infection.
authors.affiliation: Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD USA.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Srinivasa M
authors.initials: SM
authors.lastname: Srinivasula
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002479:Inclusion Bodies / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D008954:Models, Biological; D000071456:Sequestosome-1 Protein; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008070:Lipopolysaccharides; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D051197:Toll-Like Receptor 4