During hypoxia, HUMMR joins the mitochondrial dance
During hypoxia, HUMMR joins the mitochondrial dance
复制标题
DOI：
10.4161/cc.9.1.10318
复制
发表时间：
2010-01-01
期刊：
影响因子：
4.3
通讯作者：
Rempe, David A.
中科院分区：
文献类型：
--
作者：
Li, Yan;Rempe, David A.
线粒体的分布与细胞功能密切相关。高度极化的细胞，如神经元，可能依赖线粒体运输来维持正常的突触功能和轴突的可塑性。在某些情况下，线粒体转运也是细胞迁移和非神经细胞中适当的钙信号传递所必需的。在过去的几年里，在识别控制线粒体运输和分布的蛋白质方面取得了很大进展。Miro和Milton是两种线粒体外膜蛋白，它们将线粒体与运动蛋白马达蛋白捆绑在一起。我们最近的工作发现了一种新的蛋白质，HUMMR，它与Miro相互作用。在常氧条件下，HUMMR蛋白的丰度显著地通过HIF-1依赖的机制被缺氧诱导。HUMMR功能的下调会减少轴突中的线粒体数量，这一影响在暴露于低氧的神经元中更为明显。有趣的是，在低氧神经元中，击倒HUMMR也减少了顺行移动的线粒体的数量，但增加了逆行移动的线粒体的数量。因此，HUMMR是一种蛋白质，它使线粒体在缺氧时沿顺行方向移动。缺氧期间线粒体的这种偏向运输对神经元功能和生存能力的影响尚不清楚。无论如何，由于在缺血和实体瘤中缺氧是突出的，HUMMR在这些条件下可能有助于线粒体的分布。因此，HUMMR可能影响依赖于正确的线粒体定位的细胞功能。
Mitochondrial distribution is integrally related to cellular function. Highly polarized cells, such as neurons, likely depend on mitochondrial transport to maintain proper synaptic function and neurite plasticity. In some cases, mitochondrial transport is also required for cellular migration and proper calcium signaling in non-neuronal cells. Over the past few years, much progress has been made in identifying proteins that control mitochondrial transport and distribution. Miro and Milton, which are two outer mitochondrial membrane proteins, tether mitochondria to kinesin motor proteins. Our recent work identified a novel protein, HUMMR, which interacts with Miro. While present in normoxia, HUMMR protein abundance is markedly induced by hypoxia through a HIF-1 dependent mechanism. Knock down of HUMMR function diminishes the number of mitochondria in the axon, an effect that was more prominent in neurons exposed to hypoxia. Interestingly, in hypoxic neurons, knock down of HUMMR also diminished the number of anterograde moving mitochondria, but increased the number of retrograde moving mitochondria. Thus, HUMMR is a protein which biases mitochondrial movement in the anterograde direction in response to hypoxia. The implication for this biased transport of mitochondria during hypoxia on neuronal function and viability is yet to be discerned. Regardless, since hypoxia is prominent during ischemia and in solid tumors, HUMMR likely contributes to mitochondrial distribution under these conditions. As such, HUMMR may influence cellular function that is dependent upon the correct mitochondrial localization.