What can mitochondrial heterogeneity tell us about mitochondrial dynamics and autophagy?
What can mitochondrial heterogeneity tell us about mitochondrial dynamics and autophagy?
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DOI：
10.1016/j.biocel.2009.06.006
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
J. Wikstrom;G. Twig;O. Shirihai
中科院分区：
文献类型：
--
作者：
J. Wikstrom;G. Twig;O. Shirihai
越来越多的证据表明线粒体在结构和功能上是异质的。许多疾病模型都证明了异质性的增加，包括缺血再灌注和营养诱导的β细胞功能障碍和糖尿病。亚细胞位置和与其他细胞器的接近程度以及呼吸成分的不均匀分布被认为是异质性基础水平的主要贡献者。最近的研究指出线粒体动力学和自噬是线粒体异质性的主要调节因素。线粒体融合混合了线粒体网络的内容，而裂变则解剖了线粒体网络并产生去极化片段。这些去极化的线粒体与网络群体分离，形成一个有助于异质性的自噬前池。网络通过裂变事件产生去极化子体线粒体的能力对于异质性的产生至关重要。这里提出的几项研究和数据提供了一个潜在的解释，表明蛋白质和膜结构在单个线粒体内分布不均匀，并且内膜成分在融合过程中不会像基质成分那样混合。总之，线粒体亚细胞异质性反映了线粒体生命周期，涉及频繁的融合事件，其中成分可能不均匀混合，随后发生裂变事件，产生不同的子线粒体，其中一些可能再次融合，另一些将保持孤立并加入自噬前池。
A growing body of evidence shows that mitochondria are heterogeneous in terms of structure and function. Increased heterogeneity has been demonstrated in a number of disease models including ischemia-reperfusion and nutrient-induced beta cell dysfunction and diabetes. Subcellular location and proximity to other organelles, as well as uneven distribution of respiratory components have been considered as the main contributors to the basal level of heterogeneity. Recent studies point to mitochondrial dynamics and autophagy as major regulators of mitochondrial heterogeneity. While mitochondrial fusion mixes the content of the mitochondrial network, fission dissects the mitochondrial network and generates depolarized segments. These depolarized mitochondria are segregated from the networking population, forming a pre-autophagic pool contributing to heterogeneity. The capacity of a network to yield a depolarized daughter mitochondrion by a fission event is fundamental to the generation of heterogeneity. Several studies and data presented here provide a potential explanation, suggesting that protein and membranous structures are unevenly distributed within the individual mitochondrion and that inner membrane components do not mix during a fusion event to the same extent as the matrix components do. In conclusion, mitochondrial subcellular heterogeneity is a reflection of the mitochondrial lifecycle that involves frequent fusion events in which components may be unevenly mixed and followed by fission events generating disparate daughter mitochondria, some of which may fuse again, others will remain solitary and join a pre-autophagic pool.