Metabolic Interplay between Peroxisomes and Other Subcellular Organelles Including Mitochondria and the Endoplasmic Reticulum.
Metabolic Interplay between Peroxisomes and Other Subcellular Organelles Including Mitochondria and the Endoplasmic Reticulum.
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DOI：
10.3389/fcell.2015.00083
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发表时间：
2015
影响因子：
5.5
通讯作者：
Ferdinandusse S
中科院分区：
文献类型：
--
作者：
Wanders RJ;Waterham HR;Ferdinandusse S
过氧化物酶体是一种独特的亚细胞器，在几个关键的代谢途径中发挥着不可或缺的作用，包括：（1）醚磷脂生物合成;（2.）脂肪酸β-氧化;（3.）胆汁酸合成;（4.）二十二碳六烯酸（DHA）合成;（5.）脂肪酸α-氧化;（6.）乙醛酸代谢;（7.）氨基酸降解，和（8.）ROS/RNS代谢。过氧化物酶体对人类健康和发育的重要性通过存在大量过氧化物酶体代谢的先天性缺陷来例证，其中过氧化物酶体的一种或多种代谢功能受损。虽然受影响患者的临床体征和症状因缺乏的酶和缺乏程度而异，但所涉及的疾病通常是（非常）严重的疾病，其中许多人患有神经功能障碍和早期死亡。关于过氧化物酶体在代谢中的作用，很明显，过氧化物酶体依赖于与其他亚细胞器的功能相互作用来维持其在代谢中的作用。事实上，尽管线粒体可以将脂肪酸一直氧化为CO2和H2O，但过氧化物酶体只能缩短脂肪酸的链，并且过氧化物酶体β-氧化的终产物需要穿梭到线粒体以完全氧化为CO2和H2O。此外，NADH在过氧化物酶体中的β-氧化过程中产生，并且只有当过氧化物酶体配备有将NADH再氧化回NAD+的机制时，β-氧化才能继续，现在已知这是由特定的NAD（H）-氧化还原梭介导的。在本文中，我们描述了目前的知识状态过氧化物酶体和其他亚细胞区室之间的功能相互作用，特别是线粒体和内质网的每一个代谢途径，其中过氧化物酶体参与。
Peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways which include: (1.) etherphospholipid biosynthesis; (2.) fatty acid beta-oxidation; (3.) bile acid synthesis; (4.) docosahexaenoic acid (DHA) synthesis; (5.) fatty acid alpha-oxidation; (6.) glyoxylate metabolism; (7.) amino acid degradation, and (8.) ROS/RNS metabolism. The importance of peroxisomes for human health and development is exemplified by the existence of a large number of inborn errors of peroxisome metabolism in which there is an impairment in one or more of the metabolic functions of peroxisomes. Although the clinical signs and symptoms of affected patients differ depending upon the enzyme which is deficient and the extent of the deficiency, the disorders involved are usually (very) severe diseases with neurological dysfunction and early death in many of them. With respect to the role of peroxisomes in metabolism it is clear that peroxisomes are dependent on the functional interplay with other subcellular organelles to sustain their role in metabolism. Indeed, whereas mitochondria can oxidize fatty acids all the way to CO2 and H2O, peroxisomes are only able to chain-shorten fatty acids and the end products of peroxisomal beta-oxidation need to be shuttled to mitochondria for full oxidation to CO2 and H2O. Furthermore, NADH is generated during beta-oxidation in peroxisomes and beta-oxidation can only continue if peroxisomes are equipped with a mechanism to reoxidize NADH back to NAD+, which is now known to be mediated by specific NAD(H)-redox shuttles. In this paper we describe the current state of knowledge about the functional interplay between peroxisomes and other subcellular compartments notably the mitochondria and endoplasmic reticulum for each of the metabolic pathways in which peroxisomes are involved.