New Yeast Model Reveals Insights on Proteasome and Mitochondrial Interaction

A groundbreaking study conducted by the Center for Redox Processes in Biomedicine (Redoxoma), led by Marilene Demasi from the Butantan Institute in São Paulo, Brazil, has introduced a novel experimental model utilizing yeast to investigate the intricate interactions between the proteasome and mitochondrial function. This research, published in the *Archives of Biochemistry and Biophysics* on June 30, 2025, highlights the vital role of the proteasome, a protein complex in eukaryotic cells responsible for degrading damaged and nonfunctional proteins, in maintaining cellular homeostasis.

The proteasome's relationship with mitochondria has garnered increasing attention, as recent studies suggest that these two cellular components are more interconnected than previously understood. Specifically, the proteasome is instrumental in the quality control of proteins destined for the mitochondria, whereas mitochondrial metabolism can influence the efficiency of protein degradation.

In their research, the Redoxoma team examined the effects of proteasome dysfunction in the C76S mutant strain of *Saccharomyces cerevisiae*. Their findings revealed that deficiencies in the proteasome lead to an increase in mitochondrial oxidative stress, marked by elevated hydrogen peroxide (H2O2) release and a decrease in peroxiredoxin 1 (Prx1) levels. Prx1 serves as a crucial enzyme in the detoxification of peroxides, and its equivalent in mammals, Prx3, plays a similar role in mitochondrial protection.

"The significance of this work lies in the establishment of a yeast strain as a model for studying proteasome deficiency in relation to mitochondrial metabolism, a model that was previously absent in scientific literature," stated Dr. Marilene Demasi, a researcher at the Butantan Institute.

The study's implications extend beyond the immediate findings; researchers now aim to uncover the mechanisms behind the observed decrease in Prx1 levels in cells with compromised proteasomes. Dr. Demasi noted, "We are exploring whether there is a reduction in Prx1 gene expression, which is plausible as the proteasome also participates in regulating gene transcription, or if the protein undergoes hyperoxidation leading to increased degradation. The accumulation of peroxide may continuously promote its degradation."

To further elucidate these mechanisms, the research team plans to conduct comparative transcriptome and proteomic analyses of the wild-type and mutant strains cultivated under respiratory conditions. This work aims to solidify the new yeast model as an effective platform for exploring the role of the ubiquitin-proteasome system in cellular metabolism.

The findings from this study could have far-reaching implications for understanding mitochondrial dysfunctions associated with various diseases, including neurodegenerative disorders and metabolic syndromes. As the research progresses, the scientific community eagerly anticipates further insights into the proteasome's role in cellular health and disease.

In conclusion, the innovative yeast model presented by the Redoxoma team not only sheds light on the complex interplay between the proteasome and mitochondrial function but also opens new avenues for research that may lead to therapeutic strategies addressing mitochondrial-related pathologies.