# PM10 Disrupts Mitochondrial Homeostasis in Corneal Epithelial Cells: Protective Effects of SKQ1

## TL;DR

PM10 harms corneal cells by damaging mitochondria, but SKQ1 can protect against this damage.

## Contribution

This study is the first to show PM10 disrupts mitochondrial homeostasis in corneal cells and that SKQ1 offers protection.

## Key findings

- PM10 impairs mitochondrial function and reduces respiration in corneal epithelial cells.
- SKQ1 pre-treatment significantly reverses PM10-induced mitochondrial dysfunction.
- PM10 exposure alters mitochondrial fusion and fission proteins, leading to fragmentation.

## Abstract

Airborne particulate matter with a diameter of <10 μm (PM10) can damage the corneal epithelium by inducing oxidative stress, disrupting the NRF2 antioxidant pathway, and triggering epithelial barrier dysfunction and inflammation. However, the role of mitochondria in mediating PM10-induced damage remains unexplored. This study investigated the impact of PM10 on mitochondrial homeostasis in both immortalized human corneal epithelial cells (HCE-2) and the mouse corneal epithelium, as well as the protective effects of SKQ1. For in vivo assessment, female C57BL/6 mice were exposed to either control air or PM10 (±SKQ1) in a whole-body exposure chamber for 2 weeks (3 h/day, 5 days/week, with weekends off). In vitro, HCE-2 cells were exposed to 100 μg/mL PM10 (±SKQ1) for 24 h, and mitochondrial function and morphology were evaluated. In vitro, PM10 significantly impaired mitochondrial function by reducing basal, maximal, and ATP-linked respiration; reserve capacity; and coupling efficiency compared to the control and SKQ1 groups. PM10 also downregulated mitofusin1 (MFN1) and optic atrophy1 (OPA1) and upregulated dynamin-related protein1 (DRP1) and mitochondrial fission protein1 (FIS1) in HCE-2 cells. In addition, PM10 exposure significantly decreased the mitochondrial membrane potential; mitochondrial DNA copy number; and cytochrome c oxidase subunit 4 isoform 1 (COX4i1), mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) levels. SKQ1 pre-treatment significantly attenuated these effects. In vivo, PM10 exposure significantly decreased the levels of MFN1, TFAM, COX4i1, and superoxide dismutase (SOD2), whereas SKQ1 treatment significantly reversed these effects. Overall, these findings demonstrate that PM10 exposure induces mitochondrial fragmentation, disrupts mitochondrial biogenesis and quality control, and reduces mitochondrial respiration, resulting in mitochondrial dysfunction. SKQ1 effectively reversed these changes, suggesting its potential as a therapeutic strategy to protect corneal epithelial cells from PM10-induced mitochondrial damage.