Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Trends Neurosci. 2022 Apr;45(4):312-322. doi: 10.1016/j.tins.2022.01.005.
Neurons rely heavily on properly regulated mitochondrial and lysosomal homeostasis, with multiple neurodegenerative diseases linked to dysfunction in these two organelles. Interestingly, mitochondria-lysosome membrane contact sites have been identified as a key pathway mediating their crosstalk in neurons. Recent studies have further elucidated the regulation of mitochondria-lysosome contact dynamics via distinct tethering/untethering protein machinery. Moreover, this pathway has been shown to have additional functions in regulating organelle network dynamics and metabolite transfer between lysosomes and mitochondria. In this review, we highlight recent advances in the field of mitochondria-lysosome contact sites and their misregulation across multiple neurodegenerative disorders, which further underscore a potential role for this pathway in neuronal homeostasis and disease.
神经元严重依赖于线粒体和溶酶体的稳态调节，多种神经退行性疾病与这两个细胞器的功能障碍有关。有趣的是，线粒体-溶酶体膜接触位点已被确定为介导神经元中它们相互作用的关键途径。最近的研究进一步阐明了通过不同的连接/解连接蛋白机制来调节线粒体-溶酶体接触动力学。此外，该途径已被证明在调节细胞器网络动力学和溶酶体与线粒体之间的代谢物转移方面具有额外的功能。在这篇综述中，我们强调了线粒体-溶酶体接触位点及其在多种神经退行性疾病中的失调方面的最新进展，这进一步强调了该途径在神经元稳态和疾病中的潜在作用。
