Iwata Jun-ichi, Ezaki Junji, Komatsu Masaaki, Yokota Sadaki, Ueno Takashi, Tanida Isei, Chiba Tomoki, Tanaka Keiji, Kominami Eiki
Department of Biochemistry, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
J Biol Chem. 2006 Feb 17;281(7):4035-41. doi: 10.1074/jbc.M512283200. Epub 2005 Dec 6.
Peroxisomes are degraded by autophagic machinery termed "pexophagy" in yeast; however, whether this is essential for peroxisome degradation in mammals remains unknown. Here we have shown that Atg7, an essential gene for autophagy, plays a pivotal role in the degradation of excess peroxisomes in mammals. Following induction of peroxisomes by a 2-week treatment with phthalate esters in control and Atg7-deficient livers, peroxisomal degradation was monitored within 1 week after discontinuation of phthalate esters. Although most of the excess peroxisomes in the control liver were selectively degraded within 1 week, this rapid removal was exclusively impaired in the mutant liver. Furthermore, morphological analysis revealed that surplus peroxisomes, but not mutant hepatocytes, were surrounded by autophagosomes in the control. Our results indicated that the autophagic machinery is essential for the selective clearance of excess peroxisomes in mammals. This is the first direct evidence for the contribution of autophagic machinery in peroxisomal degradation in mammals.
在酵母中，过氧化物酶体通过称为“过氧化物酶体自噬”的自噬机制降解；然而，这在哺乳动物过氧化物酶体降解中是否至关重要仍不清楚。在此我们表明，自噬必需基因Atg7在哺乳动物过量过氧化物酶体的降解中起关键作用。在用邻苯二甲酸酯对对照和Atg7缺陷型肝脏进行为期2周的处理以诱导过氧化物酶体后，在停止使用邻苯二甲酸酯后的1周内监测过氧化物酶体的降解情况。尽管对照肝脏中大多数过量的过氧化物酶体在1周内被选择性降解，但这种快速清除在突变肝脏中完全受损。此外，形态学分析显示，在对照中，多余的过氧化物酶体而非突变肝细胞被自噬体包围。我们的结果表明，自噬机制对于哺乳动物中过量过氧化物酶体的选择性清除至关重要。这是自噬机制在哺乳动物过氧化物酶体降解中起作用的首个直接证据。
