Zorzano Antonio, Sebastián David, Segalés Jessica, Palacín Manuel
Institute for Research in Biomedicine, Barcelona, Spain.
Curr Opin Drug Discov Devel. 2009 Sep;12(5):597-606.
The mitochondria form dynamic organized networks or filaments that are controlled by fusion and fission events. A balance between mitochondrial fusion and fission is crucial for the correct function of these organelles. Thus, a detailed characterization of the proteins involved in mitochondrial fusion and fission, and the study of the mechanisms that regulate these two processes, would contribute to elucidating how this balance is achieved. In this regard, alterations in some of the proteins that participate in mitochondrial dynamics are linked to human pathology. In addition, experimental data support the view that mitochondrial metabolism is regulated via the manipulation of the proteins involved in mitochondrial dynamics, particularly the mitofusin 2 protein. This review evaluates the potential of mitochondrial fusion and fission proteins as targets for drug discovery, with an emphasis on mitofusin 2. The pharmacological modulation of mitochondrial dynamics may be beneficial for the treatment of specific disorders of mitochondrial dynamics and mitochondrial-inherited diseases, as well as in complex diseases with a central mitochondrial dysfunction.
线粒体形成由融合和裂变事件控制的动态有组织的网络或细丝。线粒体融合与裂变之间的平衡对于这些细胞器的正确功能至关重要。因此，详细表征参与线粒体融合与裂变的蛋白质，以及研究调节这两个过程的机制，将有助于阐明这种平衡是如何实现的。在这方面，参与线粒体动力学的一些蛋白质的改变与人类病理学有关。此外，实验数据支持这样一种观点，即线粒体代谢是通过操纵参与线粒体动力学的蛋白质，特别是线粒体融合蛋白2来调节的。本综述评估了线粒体融合和裂变蛋白作为药物发现靶点的潜力，重点是线粒体融合蛋白2。线粒体动力学的药理学调节可能有利于治疗线粒体动力学的特定疾病和线粒体遗传性疾病，以及具有中心线粒体功能障碍的复杂疾病。
