• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Mitochondrial NUDIX hydrolases: A metabolic link between NAD catabolism, GTP and mitochondrial dynamics
【24h】

Mitochondrial NUDIX hydrolases: A metabolic link between NAD catabolism, GTP and mitochondrial dynamics

机译：线粒体Nudix水解酶：NAD分解代谢，GTP和线粒体动力学之间的代谢联系

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Abstract NAD + catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD + catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism. Mitochondrial and cytosolic NUDIX hydrolases (NUDT9α and NUDT9β) can affect mitochondrial and cellular AMP levels by hydrolyzing ADP- ribose (ADPr) and subsequently altering the levels of GTP and ATP. Poly (ADP-ribose) polymerase 1 (PARP1) is activated after DNA damage, which depletes NAD + pools and results in the PARylation of nuclear and mitochondrial proteins. In the mitochondria, ADP-ribosyl hydrolase-3 (ARH3) hydrolyzes PAR to ADPr, while NUDT9α metabolizes ADPr to AMP. Elevated AMP levels have been reported to reduce mitochondrial ATP production by inhibiting the adenine nucleotide translocase (ANT), allosterically activating AMPK by altering the cellular AMP: ATP ratio, and by depleting mitochondrial GTP pools by being phosphorylated by adenylate kinase 3 (AK3), which uses GTP as a phosphate donor. Recently, activated AMPK was reported to phosphorylate mitochondria fission factor (MFF), which increases Drp1 localization to the mitochondria and promotes mitochondrial fission. Moreover, the increased AK3 activity could deplete mitochondrial GTP pools and possibly inhibit normal activity of GTP-dependent fusion enzymes, thus altering mitochondrial dynamics. Highlights ? A link between NAD + catabolism and mitochondrial dynamics is proposed. ? The mechanism is centered around elevated AMP due to NUDIX enzymes activity. ? The mechanism also supports the idea of an intra-mitochondrial PARP1. ? Phosphorylation of mitochondrial AMP depletes GTP levels, inhibiting fusion. ? Elevated AMP also activates AMPK, leading to Drp1 induced fission.
机译：摘要NAD +分解代谢和线粒体动力学是正常线粒体功能的重要部分，据报道既又造成衰老，神经变性疾病和急性脑损伤。虽然这两个过程都被广泛研究了，但几乎没有报道这两个过程的机制如何链接。本综述重点是Nudix水解酶下游NAD +分解代谢性如何影响病理条件下的线粒体动态。另外，讨论了线粒体功能障碍和碎裂中的几种潜在靶标，包括线粒体聚（ADP-核糖）聚合酶1（MTPARP1），AMPK，AMP和线粒体内的角质化GTP代谢的作用。线粒体和细胞溶质NUDIX水解酶（NUDT9α和NUDT9β）可以通过水解ADP-核糖（ADPR）并随后改变GTP和ATP的水平来影响线粒体和细胞AMP水平。聚合（ADP-核糖）聚合酶1（PARP1）在DNA损伤后被激活，其耗尽NAD +池并导致核和线粒体蛋白的粉状。在线粒体中，ADP-核糖基水解酶-3（ARH3）水解对ADPR，而NUDT9α将ADPR代谢到AMP。据报道，通过抑制细胞amp：ATP比率，通过抑制腺嘌呤核苷酸易转化酶（ANT），通过改变细胞AMP：ATP比率，通过通过腺苷激酶3（ak3）磷酸化来减少模肽核苷酸易位酶（蚂蚁），通过磷酸化，通过抑制细胞AMP：ATP比率来减少线粒体ATP水平。使用GTP作为磷酸盐供体。最近，将活性的AMPK报告给磷酸化线粒体裂变因子（MFF），其增加DRP1对线粒体的定位并促进线粒体裂变。此外，AK3活性的增加可以消耗线粒体GTP池，并且可能抑制GTP依赖性融合酶的正常活动，从而改变线粒体动力学。强调 ？提出了NAD +分解代谢和线粒体动力学之间的联系。还由于Nudix酶活性，该机制围绕升高的放大器。还该机制还支持线粒体内PARP1的想法。还线粒体AMP的磷酸化耗尽GTP水平，抑制融合。还升高的AMP还激活了AMPK，导致DRP1诱导裂变。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号