Mitochondrial fission is a critical modulator of mutant APP-induced neural toxicity.
Mitochondrial fission is a critical modulator of mutant APP-induced neural toxicity.
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DOI：
10.1016/j.jbc.2021.100469
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Nakamura K
中科院分区：
文献类型：
--
作者：
Shields LY;Li H;Nguyen K;Kim H;Doric Z;Garcia JH;Gill TM;Haddad D;Vossel K;Calvert M;Nakamura K
线粒体分裂的改变可能导致几种神经退行性疾病的病理生理学，包括阿尔茨海默病（AD）。然而，我们对裂变的正常功能或裂变破坏如何与AD相关蛋白相互作用以调节发病机制知之甚少。在这里，我们表明，中央线粒体分裂蛋白动力相关蛋白1（Drp1）在CA1和其他前脑神经元的损失显着的学习和记忆的小鼠表达突变的人淀粉样前体蛋白（hAPP）的神经元。在培养的神经元中，Drp1KO和hAPP会聚以产生线粒体Ca2+（mitoCa2+）过载，尽管减少了与线粒体相关的ER膜（MAMs）和胞质Ca2+。这种线粒体Ca2+超载的发生与ATP水平无关。这些发现揭示了线粒体分裂保护免受hAPP驱动的病理的潜在机制。
Alterations in mitochondrial fission may contribute to the pathophysiology of several neurodegenerative diseases, including Alzheimer’s disease (AD). However, we understand very little about the normal functions of fission or how fission disruption may interact with AD-associated proteins to modulate pathogenesis. Here we show that loss of the central mitochondrial fission protein dynamin-related protein 1 (Drp1) in CA1 and other forebrain neurons markedly worsens the learning and memory of mice expressing mutant human amyloid precursor protein (hAPP) in neurons. In cultured neurons, Drp1KO and hAPP converge to produce mitochondrial Ca2+ (mitoCa2+) overload, despite decreasing mitochondria-associated ER membranes (MAMs) and cytosolic Ca2+. This mitoCa2+ overload occurs independently of ATP levels. These findings reveal a potential mechanism by which mitochondrial fission protects against hAPP-driven pathology.
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影响因子：
2.8
作者：
Abdul-Khabir W;Hall T;Swanson AN;Shoptaw S
通讯作者：
Shoptaw S
影响因子：
11.4
作者：
Area-Gomez, Estela;Castillo, Maria Del Carmen Lara;Tambini, Marc D.;Guardia-Laguarta, Cristina;de Groof, Ad J. C.;Madra, Moneek;Ikenouchi, Junichi;Umeda, Masato;Bird, Thomas D.;Sturley, Stephen L.;Schon, Eric A.
通讯作者：
Schon, Eric A.
影响因子：
--
作者：
Granatiero, Veronica;Pacifici, Marco;Rizzuto, Rosario
通讯作者：
Rizzuto, Rosario
影响因子：
12.4
作者：
Estaquier, J.;Arnoult, D.
通讯作者：
Arnoult, D.
DOI：
10.1073/pnas.1006586107
发表时间：
2010-10-26
影响因子：
11.1
作者：
Du, Heng;Guo, Lan;Yan, Shirley ShiDu
通讯作者：
Yan, Shirley ShiDu