Altered fusion dynamics underlie unique morphological changes in mitochondria during hypoxia-reoxygenation stress.
Altered fusion dynamics underlie unique morphological changes in mitochondria during hypoxia-reoxygenation stress.
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DOI：
10.1038/cdd.2011.13
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发表时间：
2011-10
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
作者：
线粒体的功能状态通常反映在线粒体的特征形态上。缺氧-再氧化是最基本的应激条件之一，已知会导致线粒体功能受损并伴有结构异常，但其潜在机制有待进一步研究。在这里，我们实时监测生物能量学和线粒体融合-裂变，以确定线粒体动力学的变化如何导致缺氧再氧化过程中的结构异常。缺氧-再氧化导致线粒体缩短，融合活性降低。这种融合抑制是ATP合成受损的结果，而不是Opa1切割的结果。在无葡萄糖培养基缺氧和含葡萄糖培养基再氧化过程中出现的一个显著特征是环状线粒体的形成。甜甜圈的形成是由通透性过渡孔或K+通道的打开触发的，这反过来又导致线粒体肿胀和部分脱离细胞骨架。这有利于异常融合事件（自动融合和2-3个线粒体中几个位点的融合）产生特征的甜甜圈。甜甜圈可以有效地耐受基质体积的增加，并产生可以重新获得ΔΨm的后代。因此，缺氧-再氧化过程中的代谢应激通过诱导线粒体动力学的不同模式来改变线粒体形态，其中包括有助于线粒体适应和功能恢复的过程。
Functional states of mitochondria are often reflected in characteristic mitochondrial morphology. One of the most fundamental stress conditions, hypoxia–reoxygenation has been known to cause impaired mitochondrial function accompanied by structural abnormalities, but the underlying mechanisms need further investigation. Here, we monitored bioenergetics and mitochondrial fusion–fission in real time to determine how changes in mitochondrial dynamics contribute to structural abnormalities during hypoxia–reoxygenation. Hypoxia–reoxygenation resulted in the appearance of shorter mitochondria and a decrease in fusion activity. This fusion inhibition was a result of impaired ATP synthesis rather than Opa1 cleavage. A striking feature that appeared during hypoxia in glucose-free and during reoxygenation in glucose-containing medium was the formation of donut-shaped (toroidal) mitochondria. Donut formation was triggered by opening of the permeability transition pore or K+ channels, which in turn caused mitochondrial swelling and partial detachment from the cytoskeleton. This then favored anomalous fusion events (autofusion and fusion at several sites among 2–3 mitochondria) to produce the characteristic donuts. Donuts effectively tolerate matrix volume increases and give rise to offspring that can regain ΔΨm. Thus, the metabolic stress during hypoxia–reoxygenation alters mitochondrial morphology by inducing distinct patterns of mitochondrial dynamics, which includes processes that could aid mitochondrial adaptation and functional recovery.
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影响因子：
10.8
作者：
Chen, Le;Gong, Qizhi;Knowlton, Anne A.
通讯作者：
Knowlton, Anne A.
影响因子：
9.2
作者：
De Vos, KJ;Allan, VJ;Sheetz, MP
通讯作者：
Sheetz, MP
影响因子：
4.8
作者：
PFEIFFER, DR;GUDZ, TI;ERDAHL, WL
通讯作者：
ERDAHL, WL
DOI：
10.1016/s0006-291x(03)00050-0
发表时间：
2003-02-21
影响因子：
3.1
作者：
Ishihara, N;Jofuku, A;Mihara, K
通讯作者：
Mihara, K
影响因子：
16
作者：
Csordás G;Várnai P;Golenár T;Roy S;Purkins G;Schneider TG;Balla T;Hajnóczky G
通讯作者：
Hajnóczky G