# Mitochondrial dysfunction alters early endosome trafficking via microtubule reorganization

## TL;DR

Mitochondrial dysfunction disrupts early endosome trafficking by altering microtubules through reactive oxygen species.

## Contribution

The study reveals a novel link between mitochondrial ROS and microtubule-mediated endosomal trafficking.

## Key findings

- Mitochondrial inhibition causes early endosome aggregation and impaired lysosomal cargo delivery.
- ROS-mediated microtubule and centrosome changes underlie endosomal trafficking defects.
- Antioxidants can reverse these effects, highlighting mitochondria's role in cellular homeostasis.

## Abstract

This study shows that reactive oxygen species produced by mitochondria alter centrosome duplication, causing microtubule rearrangements that alter endosomal trafficking.

Mitochondria are essential for bioenergetics and cellular processes including cell differentiation and immunity; alterations in these processes cause a wide range of muscular and neurological pathologies. Although these pathologies have traditionally been associated with ATP deficits, mitochondrial dysfunction also leads to reactive oxygen species (ROS) generation, inflammation, and alterations in the function of other organelles. Although the negative impact of mitochondrial dysfunction on lysosomal activity is 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 ROS-mediated alterations in microtubule architecture and centrosome dynamics. 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 mitochondria’s critical involvement in cellular activities and suggest novel targets for therapies to mitigate the effects of mitochondrial dysfunction.