Optical imaging of mitochondrial function uncovers actively propagating waves of mitochondrial membrane potential collapse across intact heart.
Optical imaging of mitochondrial function uncovers actively propagating waves of mitochondrial membrane potential collapse across intact heart.
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DOI：
10.1016/j.yjmcc.2010.07.002
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发表时间：
2010-10
影响因子：
5
通讯作者：
Akar FG
中科院分区：
文献类型：
--
作者：
Lyon AR;Joudrey PJ;Jin D;Nass RD;Aon MA;O'Rourke B;Akar FG
线粒体膜电位 (ΔΨm) 的极化对于正常线粒体功能和细胞能量学至关重要。线粒体功能障碍，表现为 ΔΨm 极化破坏（即去极化或超极化），是多种重要且高度流行的疾病的基础，包括各种心脏和神经系统疾病。因此，ΔΨm 不稳定性可能形成影响可兴奋组织的一类代谢紊乱的统一机制。在这里，我们使用高分辨率光学 ΔΨm 成像测量了完整心脏中 ΔΨm 变化的时空动力学，并发现了令人惊讶的复杂空间模式和 ΔΨm 的动态波动变化，这些变化在整体缺血期间发展为积极传播的线粒体去极化波。我们的数据进一步表明，再灌注时 ΔΨm 的恢复取决于之前缺血性损伤的持续时间。缺血后电和功能恢复取决于早期 ΔΨm 恢复，但独立于使用乳酸脱氢酶释放的标准测定法测量的总体细胞损伤。这些发现揭示了一种新的机制，通过该机制，独立于不可逆细胞损伤的细胞能量特性的不稳定性可以通过涉及多细胞网络的有组织的主动传导过程扩展到完整器官的水平。这凸显了在完整器官的背景下研究细胞代谢特性的重要性。
Polarization of the mitochondrial membrane potential (ΔΨm) is critical for normal mitochondrial function and cellular energetics. Mitochondrial dysfunction, manifesting as disrupted ΔΨm polarization (i.e. depolarization or hyperpolarization), underlies several important and highly prevalent diseases, including a variety of cardiac and neurological disorders. As such, ΔΨm instability might form a unifying mechanism for a class of metabolic disorders affecting excitable tissues. Here, we measured the spatiotemporal kinetics of ΔΨm changes across the intact heart using high-resolution optical ΔΨm imaging and uncovered surprisingly complex spatial patterns and dynamically fluctuating changes in ΔΨm that developed into actively propagating waves of mitochondrial depolarization during global ischemia. Our data further indicated that the recovery of ΔΨm upon reperfusion is dictated by the duration of the preceding ischemic insult. Post-ischemic electrical and functional recovery was dependent on early ΔΨm recovery but independent of overall cellular injury measured using a standard assay of lactate dehydrogenase release. These findings reveal a novel mechanism by which instabilities in cellular energetic properties that are independent of irreversible cellular injury can scale to the level of the intact organ via an organized process of active conduction involving the multi-cellular network. This highlights the importance of investigating cellular metabolic properties in the context of the intact organ.
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影响因子：
20.1
作者：
Akar, FG;Rosenbaum, DS
通讯作者：
Rosenbaum, DS
影响因子：
3.4
作者：
Brady, NR;Elmore, SP;Westerhoff, HV
通讯作者：
Westerhoff, HV
DOI：
10.1152/ajpheart.00310.2009
发表时间：
2009-08-01
影响因子：
4.8
作者：
Park, Misun;Shen, You-Tang;Vatner, Stephen F.
通讯作者：
Vatner, Stephen F.
DOI：
10.1196/annals.1341.022
发表时间：
2005-01-01
期刊：
COMMUNICATIVE CARDIAC CELL
影响因子：
--
作者：
Honda, HM;Korge, P;Weiss, JN
通讯作者：
Weiss, JN
影响因子：
4.8
作者：
Aon, MA;Cortassa, S;O'Rourke, B
通讯作者：
O'Rourke, B