Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cell Death Differ. 2011 Oct;18(10):1561-72. doi: 10.1038/cdd.2011.13. Epub 2011 Mar 4.
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 ΔΨ(m). 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.
线粒体的功能状态通常反映在其特征性的形态上。缺氧再复氧是最基本的应激条件之一，已知它会导致线粒体功能受损，同时伴有结构异常，但具体的机制仍需要进一步研究。在这里，我们实时监测生物能量和线粒体融合-裂变，以确定线粒体动力学的变化如何导致缺氧再复氧过程中的结构异常。缺氧再复氧导致线粒体变短，融合活性降低。这种融合抑制是由于 ATP 合成受损而不是 Opa1 切割所致。在缺氧时无葡萄糖和复氧时含葡萄糖的培养基中出现的一个显著特征是形成环形（环形）线粒体。环形成是由通透性转换孔或 K(+)通道开放触发的，这反过来又导致线粒体肿胀并与细胞骨架部分分离。这有利于异常融合事件（自体融合和在 2-3 个线粒体之间的几个位点融合）产生特征性的环。环有效地耐受基质体积的增加，并产生可以恢复 ΔΨ(m)的后代。因此，缺氧再复氧过程中的代谢应激通过诱导不同的线粒体动力学模式来改变线粒体的形态，其中包括可能有助于线粒体适应和功能恢复的过程。
