Redox Regulation of Homeostasis and Proteostasis in Peroxisomes.
Redox Regulation of Homeostasis and Proteostasis in Peroxisomes.
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DOI：
10.1152/physrev.00033.2016
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发表时间：
2018
影响因子：
33.6
通讯作者：
C. Walker;L. C. Pomatto;D. Tripathi;K. Davies
中科院分区：
文献类型：
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作者：
C. Walker;L. C. Pomatto;D. Tripathi;K. Davies
过氧化物酶体是高度动态的细胞内细胞器，参与长链脂肪酸、d-氨基酸和许多多胺代谢所必需的多种代谢功能。过氧化物酶体代谢的副产物是活性氧和氮，特别是过氧化氢（H2O2）的产生和随后的解毒。由于其相对较低的反应性（作为温和氧化剂），H2O2 具有相对较长的细胞内半衰期和较高的扩散速率，所有这些使 H2O2 成为有效的信号分子。过氧化物酶体还与线粒体有着复杂的联系，这两种细胞器似乎在调节氧化还原信号通路中发挥着重要作用。过氧化物酶体蛋白也会受到它们产生的活性氧和氮的氧化修饰和失活，但过氧化物酶体LonP2蛋白酶可以选择性地去除这些氧化损伤的蛋白质，从而延长细胞器的使用寿命。过氧化物酶体稳态必须通过过氧化物酶体增殖、通过自噬（pexophagy）去除过量或严重受损的细胞器以及过氧化物酶体遗传和运动过程的组合来适应细胞的代谢状态。最近，人们发现调节 mTORC1 信号传导的肿瘤抑制因子共济失调毛细血管扩张突变 (ATM) 和结节性硬化症复合体 (TSC) 可以调节 pexophagy，以响应某些活性氧和氮物种的不同水平。现在已经清楚，过氧化物酶体稳态的任何显着丧失都可能产生毁灭性的生理后果。过氧化物酶体失调与多种代谢疾病有关，越来越多的证据强调了过氧化物酶体功能减弱在衰老过程中的重要作用。
Peroxisomes are highly dynamic intracellular organelles involved in a variety of metabolic functions essential for the metabolism of long-chain fatty acids, d-amino acids, and many polyamines. A byproduct of peroxisomal metabolism is the generation, and subsequent detoxification, of reactive oxygen and nitrogen species, particularly hydrogen peroxide (H2O2). Because of its relatively low reactivity (as a mild oxidant), H2O2 has a comparatively long intracellular half-life and a high diffusion rate, all of which makes H2O2 an efficient signaling molecule. Peroxisomes also have intricate connections to mitochondria, and both organelles appear to play important roles in regulating redox signaling pathways. Peroxisomal proteins are also subject to oxidative modification and inactivation by the reactive oxygen and nitrogen species they generate, but the peroxisomal LonP2 protease can selectively remove such oxidatively damaged proteins, thus prolonging the useful lifespan of the organelle. Peroxisomal homeostasis must adapt to the metabolic state of the cell, by a combination of peroxisome proliferation, the removal of excess or badly damaged organelles by autophagy (pexophagy), as well as by processes of peroxisome inheritance and motility. More recently the tumor suppressors ataxia telangiectasia mutate (ATM) and tuberous sclerosis complex (TSC), which regulate mTORC1 signaling, have been found to regulate pexophagy in response to variable levels of certain reactive oxygen and nitrogen species. It is now clear that any significant loss of peroxisome homeostasis can have devastating physiological consequences. Peroxisome dysregulation has been implicated in several metabolic diseases, and increasing evidence highlights the important role of diminished peroxisomal functions in aging processes.