Peroxisome structure, function, and biogenesis--human patients and yeast mutants show strikingly similar defects in peroxisome biogenesis.
Peroxisome structure, function, and biogenesis--human patients and yeast mutants show strikingly similar defects in peroxisome biogenesis.
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DOI：
10.1097/00005072-199509000-00015
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发表时间：
1995-09
影响因子：
3.2
通讯作者：
P. Lazarow
中科院分区：
文献类型：
--
作者：
P. Lazarow
过氧化物酶体存在于几乎所有的真核细胞中。细胞器的两个主要功能是脂质代谢：过氧化物酶体催化缩醛磷脂生物合成的初始步骤，缩醛磷脂是大量存在于髓鞘中的磷脂。过氧化物酶体还催化脂肪酸的β-氧化;该途径对于催化不被线粒体氧化的各种底物是必需的。第三个重要的功能是在细胞呼吸中，涉及H2 O2的代谢，过氧化物酶体因此而命名。过氧化物酶体通过翻译后从细胞质中输入新合成的蛋白质而增加大小;这些预先存在的过氧化物酶体分裂形成新的过氧化物酶体。蛋白质通过三种不同类型的局部序列靶向过氧化物酶体，并且假设每种类型都存在受体。新产生的蛋白质通过ATP水解提供能量的机制穿过过氧化物酶体膜转移到内部。人类患者和酵母突变体在过氧化物酶体生物合成中具有非常相似的缺陷。一些这样的突变体是有缺陷的过氧化物酶体蛋白的一个子集，共享一个拓扑序列类型的进口;其他突变体未能进口所有新制造的蛋白质进入过氧化物酶体，无论它们拥有的靶向序列的类型。这些突变体可能分别在受体和转运机制组件中有缺陷。过氧化物酶体生物合成所必需的克隆基因编码不同的蛋白质：一些可能的受体，一些跨膜蛋白可能参与易位，和其他亲水性蛋白，可能发挥其他作用的过氧化物酶体组装。
Peroxisomes are found in almost all eukaryotic cells. Two major functions of the organelle are in lipid metabolism: peroxisomes catalyze the initial steps in the biosynthesis of plasmalogens, which are phospholipids that are present in large amounts in myelin. Peroxisomes also catalyze the beta-oxidation of fatty acids; this pathway is essential for the catabolism of a variety of substrates that are not oxidized by mitochondria. A third important function is in cellular respiration, involving the metabolism of H2O2, for which the peroxisome is named. Peroxisomes increase in size by the post-translational import of newly synthesized proteins from the cytosol; these pre-existing peroxisomes divide to form new peroxisomes. Proteins are targeted to peroxisomes by three different types of topogenic sequences, and it is hypothesized that a receptor exists for each type. The newly made proteins are translocated through the peroxisomal membrane into the interior by a machinery that is energized by ATP hydrolysis. Human patients and yeast mutants have remarkably similar defects in peroxisome biogenesis. Some such mutants are defective in the import of a subset of peroxisomal proteins that share a topogenic sequence type; other mutants fail to import all newly made proteins into peroxisomes, regardless of the type of targeting sequence they possess. These mutants might be defective in receptors and in translocation machinery components, respectively. Cloned genes that are essential for peroxisome biogenesis encode diverse proteins: some likely receptors, some transmembrane proteins possibly involved in translocation, and others hydrophilic proteins that may play other roles in peroxisome assembly.