title: Comprehensive proteomics analysis of autophagy-deficient mouse liver.
abstract: Autophagy is a bulk protein degradation system for the entire organelles and cytoplasmic proteins. Previously, we have shown the liver dysfunction by autophagy deficiency. To examine the pathological effect of autophagy deficiency, we examined protein composition and their levels in autophagy-deficient liver by the proteomic analysis. While impaired autophagy led to an increase in total protein mass, the protein composition was largely unchanged, consistent with non-selective proteins/organelles degradation of autophagy. However, a series of oxidative stress-inducible proteins, including glutathione S-transferase families, protein disulfide isomerase and glucose-regulated proteins were specifically increased in autophagy-deficient liver, probably due to enhanced gene expression, which is induced by accumulation of Nrf2 in the nuclei of mutant hepatocytes. Our results suggest that autophagy deficiency causes oxidative stress, and such stress might be the main cause of liver injury in autophagy-deficient liver.
authors.affiliation: Department of Biochemistry, Juntendo University School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Junji
authors.initials: J
authors.lastname: Ezaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takahashi
authors.forename: Reiko
authors.initials: R
authors.lastname: Mineki
authors.forename: Hikari
authors.initials: H
authors.lastname: Taka
authors.forename: Mika
authors.initials: M
authors.lastname: Kikkawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujimura
authors.forename: Mitsue
authors.initials: M
authors.lastname: Takeda-Ezaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueno
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Eiki
authors.initials: E
authors.lastname: Kominami
mesh_terms: D000818:Animals; D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D044764:Ubiquitin-Activating Enzymes / Q000172:deficiency*
chemical_list: D006360:Heat-Shock Proteins; D020543:Proteome; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes