# N-acetyl-L-cysteine improves mitochondrial and oxidative defects in the acadian variant of fanconi syndrome

## TL;DR

This study shows that N-acetyl-L-cysteine (NAC) can reduce oxidative stress and improve mitochondrial function in a rare genetic disorder called Acadian variant of Fanconi Syndrome.

## Contribution

The first demonstration that NAC can alleviate mitochondrial and oxidative defects in AVFS.

## Key findings

- NAC treatment partially restored complex I activity and mitochondrial function in AVFS fibroblasts.
- NAC reduced oxidative damage markers in AVFS fibroblasts.
- The study identifies high oxidative stress as part of AVFS pathophysiology.

## Abstract

The Acadian variant of Fanconi Syndrome (AVFS) is a rare genetic disorder characterized by renal deficiencies. AVFS is caused by a mutation to NDUFAF6 encoding a complex I assembly factor, and leading to metabolic alterations. We confirmed that fibroblasts derived from AVFS patients have lower complex I activity, mitochondrial membrane potential and cellular respiration. These mitochondrial defects were accompanied by higher levels of 8-hydroxy-2′deoxyguanosine, malondialdehyde and carbonyl, which are markers of oxidative damage to DNA, lipids and proteins, respectively. Thus, we hypothesized that the antioxidant N-Acetyl-L-cysteine (NAC) would reduce oxidative stress and mitochondrial defects in AVFS fibroblasts. Treatment with NAC during 5 days partially restored complex I activity, mitochondrial membrane potential and cellular respiration in AVFS fibroblasts. NAC also prevented oxidative damage in AVFS fibroblasts. This work shows for the first time that the physiopathology of AVFS includes high oxidative stress. It also reveals that NAC and other antioxidant-based strategies might represent an effective pharmacological treatment for AVFS.