Comprehensive proteomics analysis of autophagy-deficient mouse liver.
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.
Matsumoto
Naomi
N
Department of Biochemistry, Juntendo University School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, Japan.
Ezaki
Junji
J
Komatsu
Masaaki
M
Takahashi
Katsuyuki
K
Mineki
Reiko
R
Taka
Hikari
H
Kikkawa
Mika
M
Fujimura
Tsutomu
T
Takeda-Ezaki
Mitsue
M
Ueno
Takashi
T
Tanaka
Keiji
K
Kominami
Eiki
E
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*
D006360:Heat-Shock Proteins; D020543:Proteome; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes