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REVIEW article

Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1527013

Novel Strategies Targeting Mitochondria-Lysosome Contact Sites for the Treatment of Neurological Diseases

Provisionally accepted
Yinyin Xie Yinyin Xie 1Sun Wenlin Sun Wenlin 1Aoya Han Aoya Han 1Xinru Zhou Xinru Zhou 1Shijie Zhang Shijie Zhang 1Changchang Shen Changchang Shen 1Yi Xie Yi Xie 1Cui Wang Cui Wang 2Nanchang Xie Nanchang Xie 1*
  • 1 Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  • 2 First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China

The final, formatted version of the article will be published soon.

    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.interactions, their underlying molecular mechanisms and physiological significance remain unclear. Future research is needed to elucidate the specific signaling pathways, regulatory proteins, and metabolic processes that govern these interactions under defined conditions and to explore their broader implications for cellular function and homeostasis.Although the mitochondrial and lysosomal membranes form specific contact sites mediated by tethering proteins, it is important to emphasize that they do not fuse, but instead maintain their distinct structures and characteristics, which are crucial for their roles as major platforms in regulating various physiological processes, such as the mitochondrial network, lysosomal dynamics, calcium homeostasis, and lipid metabolism, all of which have been implicated in Parkinson's disease (PD), Charcot-Marie-Tooth (CMT) disease, and lysosomal storage diseases (LSDs) (

    Keywords: lysosomal dynamics, mitochondria-lysosome contact sites, mitochondrial network, mitophagy, Neurological Diseases, substance exchanges

    Received: 12 Nov 2024; Accepted: 30 Dec 2024.

    Copyright: © 2024 Xie, Wenlin, Han, Zhou, Zhang, Shen, Xie, Wang and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Nanchang Xie, Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.