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bioRxiv · 10.1101/2024.08.21.608999

Mitochondrial Dysfunction alters Early Endosome Distribution and Cargo Trafficking via ROS-Mediated Microtubule Reorganization

Vishwakarma, A.·Chikhi, L.·Todkar, K.·Ouellet, M.·Germain, M.
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Abstract

Mitochondria are essential for bioenergetic functions and various cellular processes, including differentiation and immunity, their dysfunction leading to several pathologies. While these pathologies have traditionally been associated with ATP deficits, mitochondrial dysfunction also leads to reactive oxygen species (ROS) generation, inflammation, and alterations the function of other organelles. While the negative impact of mitochondrial dysfunction on lysosomal activity has been established, the relationship between mitochondria and the rest of the endocytic compartment remains poorly understood. Here, we show that inhibiting mitochondrial activity through genetic and chemical approaches causes early endosome (EE) perinuclear aggregation and impairs cargo delivery to lysosomes. This impairment is due to altered microtubule architecture and centrosome dynamics, mediated by ROS. Antioxidants can rescue these EE defects, underlying the pivotal role of mitochondria in maintaining cellular activities through ROS regulation of microtubule networks. Our findings highlight the significance of mitochondria beyond ATP production, emphasizing their critical involvement in endocytic trafficking and cellular homeostasis. These insights emphasize mitochondrias critical involvement in cellular activities and suggest novel targets for therapies to mitigate the effects of mitochondrial dysfunction.

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Vishwakarma, A., Chikhi, L., Todkar, K., Ouellet, M., Germain, M.. 2024-08-22. Mitochondrial Dysfunction alters Early Endosome Distribution and Cargo Trafficking via ROS-Mediated Microtubule Reorganization. https://doi.org/10.1101/2024.08.21.608999

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