Novel strategies targeting mitochondria-lysosome contact sites for the treatment of neurological diseases
Yinyin Xie, Wenlin Sun, Aoya Han, Xinru Zhou, Shijie Zhang, Chuchu Shen, Yi Xie, Cui Wang, Nanchang Xie
Abstract
Mitochondria and lysosomes are critical for neuronal homeostasis, as highlighted by their dysfunction in various neurological diseases. Recent studies have identified dynamic membrane contact sites between mitochondria and lysosomes, independent of mitophagy and the lysosomal degradation of mitochondrial-derived vesicles (MDVs), allowing bidirectional crosstalk between these cell compartments, the dynamic regulation of organelle networks, and substance exchanges. Emerging evidence suggests that abnormalities in mitochondria-lysosome contact sites (MLCSs) contribute to neurological diseases, including Parkinson's disease, Charcot-Marie-Tooth (CMT) disease, lysosomal storage diseases, and epilepsy. This article reviews recent research advances regarding the tethering processes, regulation, and function of MLCSs and their role in neurological diseases.