Journal
IUBMB LIFE
Volume 63, Issue 11, Pages 1001-1008Publisher
WILEY-BLACKWELL
DOI: 10.1002/iub.537
Keywords
autophagy; hypolipidemic drugs; LC3; lysosome; peroxisome
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [16590253, 19390079, 14380308, 16370063, 18076005]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [14380308, 16590253, 18076005, 19390079, 16370063] Funding Source: KAKEN
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This review summarizes the historical aspects of the study of peroxisome degradation in mammalian cells. Peroxisomes have diverse metabolic roles in response to environmental changes and are degraded in a preferential manner, by comparison with cytosolic proteins. This review introduces three hypotheses on the degradation mechanisms: (a) the action of the peroxisome-specific Lon protease; (b) the membrane disruption effect of 15-lipoxygenase; and (c) autophagy that sequesters and degrades the organelles by lysosomal enzymes. Among these hypotheses, autophagy is now recognized as the most important mechanism for excess peroxisome degradation. One of the most striking characteristics of peroxisomes is that they are markedly proliferated in the liver by the administration of hypolipidemic drugs and industrial plasticizers. The effects of these substances were fully reversed after withdrawal of the substances, and most of the excess peroxisomes were selectively degraded and recovered to a normal number and size. Autophagic degradation of peroxisomes has been examined using this characteristic phenomenon. Excessive peroxisome degradation that occurs after cessation of hypolipidemic drugs has been extensively investigated biochemically and morphologically. The evidence shows that the degradation of excess peroxisomes and peroxisomal enzymes is inhibited by 3-methyladenine (3-MA), a specific inhibitor of autophagy. Furthermore, in liver-specific autophagy- deficient mice, rapid removal of peroxisomes was exclusively impaired, and degradation of peroxisomal enzymes was not detected. Thus, the significant contribution of autophagic machinery to peroxisomal degradation in mammals was confirmed. However, the important question of the mechanism for the selective recognition of peroxisomes by autophagosomes remains to be fully elucidated. (C) 2011 IUBMB IUBMB Life, 63(11): 1001-1008, 2011
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