# Csn5 Depletion Reverses Mitochondrial Defects in GCN5-Null Saccharomyces cerevisiae

## TL;DR

Deleting the Csn5 gene in yeast reverses mitochondrial issues caused by the absence of the GCN5 gene, possibly through effects on ergosterol production.

## Contribution

This study reveals that Csn5 depletion rescues mitochondrial defects in GCN5-null yeast, linking Csn5 to ergosterol biosynthesis.

## Key findings

- Deleting CSN5 rescues mitochondrial morphology and inheritance defects in GCN5-null yeast.
- GCN5 deletion causes mitochondrial DNA copy number reduction and mitophagy activation.
- Ergosterol supplementation rescues mitochondrial defects, suggesting a role for Csn5 in ergosterol biosynthesis.

## Abstract

In this study, we investigated the mitochondrial defects resulting from the deletion of GCN5, a lysine-acetyltransferase, in the yeast Saccharomyces cerevisiae. Gcn5 serves as the catalytic subunit of the SAGA acetylation complex and functions as an epigenetic regulator, primarily acetylating N-terminal lysine residues on histones H2B and H3 to modulate gene expression. The loss of GCN5 leads to mitochondrial abnormalities, including defects in mitochondrial morphology, a reduced mitochondrial DNA copy number, and defective mitochondrial inheritance due to the depolarization of actin filaments. These defects collectively trigger the activation of the mitophagy pathway. Interestingly, deleting CSN5, which encodes to Csn5/Rri1 (Csn5), the catalytic subunit of the COP9 signalosome complex, rescues the mitochondrial phenotypes observed in the gcn5Δ strain. Furthermore, these defects are suppressed by exogenous ergosterol supplementation, suggesting a link between the rescue effect mediated by CSN5 deletion and the regulatory role of Csn5 in the ergosterol biosynthetic pathway.