Neuroprotective coordination of cell mitophagy by the F1Fo-ATPase inhibitory factor 1 (IF1)
Neuroprotective coordination of cell mitophagy by the F1Fo-ATPase inhibitory factor 1 (IF1)
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DOI：
10.1016/j.phrs.2015.10.010
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发表时间：
2016-01-01
影响因子：
9.3
通讯作者：
Campanella, Michelangelo
中科院分区：
文献类型：
--
作者：
Matic, Ivana;Cocco, Stefania;Campanella, Michelangelo
线粒体F（1）Fo-ATP酶抑制因子1（IF 1）阻断F（1）Fo-ATP合酶的逆转，以防止细胞ATP的有害消耗和相关死亡。在此，我们进一步推断其分子生理学通过评估其在神经元的保护功能，在挑战条件下的稳态respirations.By采用在体外和体内的协议缺氧/缺血和复氧，我们表明，在IF 1：F1 Fo-ATP合酶的表达比例的变化发生在神经元。这种增加的IF 1水平对于诱导PTEN诱导的推定激酶1（PINK-1）的积累和线粒体吞噬泛素连接酶PARK-2的募集以促进线粒体群体的自噬“控制”是必需的。在IF 1过表达的神经元中，缺氧缺血时ATP消耗减少，线粒体膜电位（Δ Y-m）对再氧合有弹性，并对生电、Ca ~（2+）依赖性去极化有抵抗力，这些数据表明，在哺乳动物神经元中，线粒体通过上调IF 1来适应呼吸应激，IF 1通过协调促生存细胞的线粒体自噬和生物能量学弹性发挥保护作用。(C)2015爱思唯尔有限公司出版
The mitochondrial F(1)Fo-ATPase inhibitory factor 1 (IF1) blocks the reversal of the F(1)Fo-ATPsynthase to prevent detrimental consumption of cellular ATP and associated demise. Herein, we infer further its molecular physiology by assessing its protective function in neurons during conditions of challenged homeostatic respiration.By adopting in vitro and in vivo protocols of hypoxia/ischemia and re-oxygenation, we show that a shift in the IF1:F1Fo-ATPsynthase expression ratio occurs in neurons. This increased IF1 level is essential to induce accumulation of the PTEN-induced putative kinase 1 (PINK-1) and recruitment of the mitophagic ubiquitin ligase PARK-2 to promote autophagic "control" of the mitochondrial population. In IF1 overexpressing neurons ATP depletion is reduced during hypoxiaiischemia and the mitochondrial membrane potential (Delta Y-m) resilient to re-oxygenation as well as resistant to electrogenic, Ca2+ dependent depolarization.These data suggest that in mammalian neurons mitochondria adapt to respiratory stress by upregulating IF1, which exerts a protective role by coordinating pro-survival cell mitophagy and bioenergetics resilience. (C) 2015 Published by Elsevier Ltd.