[Autophagic-lysosomal system: physiology and pathology].
There is increased evidence for the importance of autophagy as a membrane trafficking mechanism that delivers cytoplasmic constituents into the lysosome/vacuole for bulk protein degradation. In this review, we introduce the in vivo role of autophagy in mammals. Recently, we generated conditional-knockout mice of Atg7, an essential gene for autophagy in yeast. Atg7 disruption resulted in impairment of starvation-induced protein degradation in the adult liver, and Atg7-null mice died within 1 day after birth, associated with low concentrations of plasma amino acids as well as the other autophagy-essential gene, Atg5. Furthermore, loss of Atg7 led to pleiotropic defects, in particular, accumulation of abnormal organelles and ubiquitin-positive inclusions without obvious failure of proteasome function. These results indicate the important role of autophagy in starvation response and the quality control of proteins and organelles in quiescent cells.
Komatsu
Masaaki
M
Department of Biochemistry, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
Kominami
Eiki
E
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071192:Autophagy-Related Protein 12; D004435:Eating / Q000502:physiology; D006801:Humans; D008247:Lysosomes / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015388:Organelles / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins; D013217:Starvation / Q000378:metabolism
C466624:ATG12 protein, human; D000071192:Autophagy-Related Protein 12; D011506:Proteins; D025841:Small Ubiquitin-Related Modifier Proteins