# Impaired Mitochondrial Network Morphology and Reactive Oxygen Species Production in Fibroblasts from Parkinson’s Disease Patients

## TL;DR

This study shows that fibroblasts from Parkinson’s disease patients have abnormal mitochondria and increased reactive oxygen species, especially in those with specific genetic mutations.

## Contribution

The study introduces new insights into mitochondrial dysfunction in PD fibroblasts using super-resolution microscopy and image analysis.

## Key findings

- Fibroblasts with Pink1/Parkin mutations show larger mitochondrial networks with longer mitochondria.
- PINK1 and α-synuclein mutations are linked to mitochondrial hyperpolarization and higher cytosolic ROS.
- Only PINK1 and α-synuclein mutations show increased mitochondrial ROS production.

## Abstract

The mitochondrial network (MN) is a dynamic structure undergoing constant remodeling in the cell. It is assumed that perturbations to the MN may be associated with various pathologies, including Parkinson’s disease (PD). Using automatic image analysis and super-resolution microscopy, we have assessed the MN parameters in fibroblasts from patients with established hereditary PD mutations (associated with PINK1, LRRK2, and α-synuclein, as well as PINK1 and Parkin proteins simultaneously) under normal conditions and after hydrogen peroxide-induced stress. Fibroblasts with the Pink1/Parkin mutation are most different in morphology to fibroblasts obtained from conditionally healthy donors: the MN is larger, and it contains longer mitochondria and accumulated individual mitochondria. In addition to MN, we evaluated other cellular parameters, such as cytosolic and mitochondrial ROS production and mitochondrial membrane potential. It has been shown that mitochondria of fibroblasts with mutations in genes encoding PINK1, α-synuclein, and Pink/Parkin tend towards hyperpolarization and cytosolic ROS overproduction, while mitochondrial ROS production was higher only in fibroblasts with PINK1 and α-synuclein mutations.