Excess peroxisomes are degraded by autophagic machinery in mammals
Excess peroxisomes are degraded by autophagic machinery in mammals
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DOI：
10.1074/jbc.m512283200
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发表时间：
2006-02-17
影响因子：
4.8
通讯作者：
Kominami, E
中科院分区：
文献类型：
--
作者：
Iwata, J;Ezaki, J;Kominami, E
过氧化物酶体被酵母中称为“pexophagy”的自噬机制降解;然而，这是否是哺乳动物过氧化物酶体降解所必需的仍然未知。在这里，我们已经表明，Atg 7，自噬的必需基因，在哺乳动物中过量过氧化物酶体的降解中起着关键作用。在对照组和Atg 7缺陷肝脏中，通过邻苯二甲酸酯治疗2周诱导过氧化物酶体后，在邻苯二甲酸酯停药后1周内监测过氧化物酶体降解。虽然大多数过量的过氧化物酶体在对照组的肝脏在1周内选择性降解，这种快速的去除是专门受损的突变体的肝脏。此外，形态学分析显示，过剩的过氧化物酶体，但不是突变的肝细胞，被包围的自噬体在控制。我们的研究结果表明，自噬机制是必不可少的选择性清除过剩的过氧化物酶体在哺乳动物。这是自噬机制在哺乳动物过氧化物酶体降解中的贡献的第一个直接证据。
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.