Building out the FBXL4-NIX-mitophagy axis

线粒体是几乎所有人类细胞中的发电站。不时地，这些退役和新的制造。在线粒体自噬的过程中，旧的或受损的线粒体被送到细胞破体或溶酶体。线粒体自噬在发育过程中很重要，但在抑制神经变性和其他病理生理条件中也很重要。有时，线粒体自噬会过度活跃，患者体内的线粒体太少，无法满足身体的能量需求，从而患上线粒体耗竭综合征。这就是FBXL4基因突变患者的情况。最近，我们通过FBXL4控制另一种叫做NIX的蛋白质的水平，发现了这种突变是如何导致线粒体自噬过度的，这种蛋白质可以潜入线粒体，有效地充当谴责通知。现在我们想在这些发现的基础上，提供一个更完整的有丝分裂过程的观点，看看FBXL4的功能是如何与其他蛋白质和修饰一起编排的。我们的工作结合了假设驱动和更开放的基于发现的研究，这可能会导致影响线粒体健康的新方法，从而造福患者。

Mitochondria are the power stations within nearly all human cells. From time to time these are decommisoned and new ones are made. The old or damaged mitochondria are delivered to the cell breakers yard or lysosome in a process called mitophagy. Mitophagy is important in developmental pathways but also in suppressing neurodegeneration and other pathophysological conditions. Sometimes mitophagy can be over-active and patients are left with too few mitochondria for the body's energy needs and suffer from mitochondrial depletion syndrome. This is the case for patients with a mutation in a gene called FBXL4. We have recently figured out how such mutations lead to this excess of mitophagy, by showing that FBXL4 controls the levels of another protein called NIX, which can dive into the mitochondria and effectively act as a notice of condemnation. Now we want to build on these findings and provide a more integrated view of the mitophagy process that looks at how the function of FBXL4 is choreographed with other proteins and modifications. Our work combines hypothesis-driven and more open-ended discovery based research which may lead to new ways of influencing mitochondrial health for the benefit of patients.