Activity regulates a cell type-specific mitochondrial phenotype in zebrafish lateral line hair cells.
Activity regulates a cell type-specific mitochondrial phenotype in zebrafish lateral line hair cells.
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DOI：
10.7554/elife.80468
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发表时间：
2023-03-13
期刊：
影响因子：
7.7
通讯作者：
Raible DW
中科院分区：
文献类型：
--
作者：
McQuate A;Knecht S;Raible DW
内耳毛细胞对线粒体的变化特别敏感，线粒体是所有真核细胞中产生能量所必需的亚细胞细胞器。有超过30种线粒体耳聋基因，线粒体与噪音暴露后毛细胞死亡、氨基糖苷类抗生素暴露以及与年龄相关的听力损失有关。然而，对毛细胞线粒体生物学的基本方面所知甚少。利用斑马鱼侧线毛细胞作为模型和连续块面扫描电子显微镜，我们定量表征了一种独特的毛细胞线粒体表型，包括：(1)高线粒体体积和(2)特定的线粒体结构：顶部有多个小线粒体，底部有网状线粒体网络。这种表型在毛细胞的一生中逐渐发展。破坏这种线粒体表型与突变的opa1影响线粒体的健康和功能。虽然毛细胞的活动不是高线粒体体积所必需的，但它塑造了线粒体的结构，机械转导是所有模式所必需的，突触传递是线粒体网络发展所必需的。这些结果表明毛细胞高度调节线粒体以达到最佳生理状态，并为线粒体耳聋提供了新的见解。我们感知声音的能力依赖于我们耳朵深处的微小细胞，这些细胞可以将振动转化为大脑能够解码的电信号。这些“毛细胞”的一端有一小簇短纤维，可以根据压力波移动。这种活动所需的大量能量是由细胞的线粒体提供的，线粒体是细胞内部的小隔间，起着细胞发电站的作用。事实上，降低毛细胞的线粒体功能会导致听力障碍。线粒体通常被描绘成豆状，但实际上它们可以根据需要产生的能量水平采取不同的形状。尽管形态和功能之间存在这种联系，但人们对毛细胞中的线粒体是什么样子知之甚少。了解这些结构是如何支持毛细胞和健康听力的，填补这一知识空白是必要的。为了解决这个问题，McQuate等人转向了斑马鱼，因为这些动物通过皮肤上容易接近的毛细胞来探测水中的振动，这些毛细胞的工作原理就像哺乳动物耳朵里的毛细胞一样。从高分辨率显微镜获得并分析了一系列3D图像，结果显示毛细胞比其他类型的细胞更密集地聚集着线粒体。线粒体组织结构也明显不同。携带毛发状结构的细胞一侧有许多小的线粒体；然而，在与神经元接触的另一侧，线粒体形成了一个单一的大网络。不同类型的线粒体在一个细胞内共存是一个新概念。进一步的实验研究了这些线粒体特征是如何与毛细胞活动联系在一起的。他们发现，这种组织是随着细胞衰老而逐渐建立起来的，细胞活动塑造了线粒体的结构（但不是总体积）。总的来说，McQuate等人的工作为开发与线粒体功能障碍相关的听力障碍治疗方法提供了必要的重要信息。然而，通过表明不同种类的线粒体可以存在于一个细胞中，它也应该为那些专注于听力的研究提供信息。
Hair cells of the inner ear are particularly sensitive to changes in mitochondria, the subcellular organelles necessary for energy production in all eukaryotic cells. There are over 30 mitochondrial deafness genes, and mitochondria are implicated in hair cell death following noise exposure, aminoglycoside antibiotic exposure, as well as in age-related hearing loss. However, little is known about the basic aspects of hair cell mitochondrial biology. Using hair cells from the zebrafish lateral line as a model and serial block-face scanning electron microscopy, we have quantifiably characterized a unique hair cell mitochondrial phenotype that includes (1) a high mitochondrial volume and (2) specific mitochondrial architecture: multiple small mitochondria apically, and a reticular mitochondrial network basally. This phenotype develops gradually over the lifetime of the hair cell. Disrupting this mitochondrial phenotype with a mutation in opa1 impacts mitochondrial health and function. While hair cell activity is not required for the high mitochondrial volume, it shapes the mitochondrial architecture, with mechanotransduction necessary for all patterning, and synaptic transmission necessary for the development of mitochondrial networks. These results demonstrate the high degree to which hair cells regulate their mitochondria for optimal physiology and provide new insights into mitochondrial deafness. Our ability to perceive sounds relies on tiny cells deep inside our ears which can convert vibrations into the electrical signals that our brain is able to decode. These ‘hair cells’ sport a small tuft of short fibers on one of their ends that can move in response to pressure waves. The large amount of energy required for this activity is provided by the cells’ mitochondria, the small internal compartments that act as cellular powerhouses. In fact, reducing mitochondrial function in hair cells can lead to hearing disorders. Mitochondria are often depicted as being bean-like, but they can actually adopt different shapes based on the level of energy they need to produce. Despite this link between morphology and function, little is known about what mitochondria look like in hair cells. Filling this knowledge gap is necessary to understand how these structures support hair cells and healthy hearing. To address this question, McQuate et al. turned to zebrafish, as these animals detect vibrations in water through easily accessible hair cells on their skin that work just like the ones in the mammalian ear. Obtaining and analysing series of 3D images from a high-resolution microscope revealed that hair cells are more densely populated with mitochondria than other cell types. Mitochondrial organisation was also strikingly different. The side of the cell that carries the hair-like structures featured many small mitochondria; however, on the opposite side, which is in contact with neurons, the mitochondria formed a single large network. The co-existence of different types of mitochondria within one cell is a novel concept. Further experiments investigated how these mitochondrial characteristics were connected to hair cell activity. They showed that this organisation was established gradually as the cells aged, with cellular activity shaping the architecture (but not the total volume) of the mitochondria. Overall, the work by McQuate et al. provides important information necessary to develop therapeutics for hearing disorders linked to mitochondrial dysfunction. However, by showing that various kind of mitochondria can be present within one cell, it should also inform studies beyond those that focus on hearing.
影响因子：
0.9
作者：
Lesus J;Arias K;Kulaga J;Sobkiv S;Patel A;Babu V;Kambalyal A;Patel M;Padron F;Mozaffari P;Jayakumar A;Ghatalah L;Laban N;Bahari R;Perkins G;Lysakowski A
通讯作者：
Lysakowski A