Molecular insights into peroxisome homeostasis and peroxisome biogenesis disorders
Molecular insights into peroxisome homeostasis and peroxisome biogenesis disorders
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DOI：
10.1016/j.bbamcr.2022.119330
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发表时间：
2022-08-12
影响因子：
5.1
通讯作者：
Abe，Yuichi
中科院分区：
文献类型：
--
作者：
Fujiki，Yukio;Okumoto，Kanji;Abe，Yuichi
过氧化物酶体是细胞代谢所必需的单膜细胞器，包括脂肪酸的β-氧化、醚脂缩醛磷脂的合成和氧化还原稳态。对过氧化物酶体生物发生和人类过氧化物酶体生物发生障碍（PBD）的研究已经发现了14个编码参与过氧化物酶体生物发生的过氧化物的PEX基因，并且PEX基因的突变是导致PBD的原因。最近的许多发现进一步推进了我们对过氧化物酶体功能缺陷的生物学、生理学和后果的理解。在这篇综述中，我们讨论了细胞防御机制，抵消氧化应激1）促凋亡Bcl-2因子BAK介导的释放到过氧化氢降解过氧化氢酶从过氧化物酶体和2）过氧化物酶体进口抑制过氧化氢酶的丝氨酸232磷酸化的Pex 14，Pex 5-PTS 1复合物的对接蛋白。关于过氧化物酶体分裂，最近通过在低等真核生物中发现核苷二磷酸激酶样蛋白（称为DYNAMO 1）解决了如何产生和供应富含能量的GTP用于分裂过程的重要问题，DYNAMO 1具有哺乳动物同源物NME 3。在PBD发病机制方面，一种新的PBD模型小鼠Pex 14缺陷表现出脑源性神经营养因子（BDNF）-TrkB通路失调，这是小脑形态发生的重要信号通路。过氧化物酶体和其他细胞器之间的通信也得到解决。
Peroxisomes are single-membrane organelles essential for cell metabolism including the β-oxidation of fatty acids, synthesis of etherlipid plasmalogens, and redox homeostasis. Investigations into peroxisome biogenesis and the human peroxisome biogenesis disorders (PBDs) have identified 14PEXgenes encoding peroxins involved in peroxisome biogenesis and the mutation ofPEXgenes is responsible for the PBDs. Many recent findings have further advanced our understanding of the biology, physiology, and consequences of a functional deficit of peroxisomes. In this Review, we discuss cell defense mechanisms that counteract oxidative stress by 1) a proapoptotic Bcl-2 factor BAK-mediated release to the cytosol of H2O2-degrading catalase from peroxisomes and 2) peroxisomal import suppression of catalase by Ser232-phosphorylation of Pex14, a docking protein for the Pex5–PTS1 complex. With respect to peroxisome division, the important issue of how the energy-rich GTP is produced and supplied for the division process was recently addressed by the discovery of a nucleoside diphosphate kinase-like protein, termed DYNAMO1 in a lower eukaryote, which has a mammalian homologue NME3. In regard to the mechanisms underlying the pathogenesis of PBDs, a new PBD model mouse defective in Pex14 manifests a dysregulated brain-derived neurotrophic factor (BDNF)-TrkB pathway, an important signaling pathway for cerebellar morphogenesis. Communications between peroxisomes and other organelles are also addressed.