The SARS-CoV-2 main protease causes mitochondrial dysfunction in a yeast model

Abstract Saccharomyces cerevisiae has proven to be an invaluable model organism for studying mitochondrial function owing to its genetic tractability and the high conservation of mitochondrial processes among eukaryotes, including humans. Yeasts are easy to culture and manipulate genetically, which...

Full description

Saved in:
Bibliographic Details
Main Authors: Wojciech Grabiński, Anna Kicińska, Karolina Funtowicz, Tomasz Skrzypczak, Andonis Karachitos
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-11993-w
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849332843644190720
author Wojciech Grabiński
Anna Kicińska
Karolina Funtowicz
Tomasz Skrzypczak
Andonis Karachitos
author_facet Wojciech Grabiński
Anna Kicińska
Karolina Funtowicz
Tomasz Skrzypczak
Andonis Karachitos
author_sort Wojciech Grabiński
collection DOAJ
description Abstract Saccharomyces cerevisiae has proven to be an invaluable model organism for studying mitochondrial function owing to its genetic tractability and the high conservation of mitochondrial processes among eukaryotes, including humans. Yeasts are easy to culture and manipulate genetically, which allows rapid generation of mutant strains and detailed dissection of mitochondrial pathways. In addition, the ability of yeasts to survive without functional mitochondria allows the study of mutations that are lethal to organisms that are dependent on aerobic metabolism. Taking advantage of these benefits, we investigated the toxicity of SARS-CoV-2 main protease (Mpro) expression in yeast under conditions that enforce mitochondria-dependent aerobic metabolism. Our results showed that Mpro expression was highly toxic and significantly impaired yeast growth. Pronounced changes in the morphology and mitochondrial function were observed, indicating that mitochondrial pathways are exceptionally sensitive to Mpro activity. These results provide insights that may be relevant for understanding the effects of Mpro in more complex eukaryotic systems.
format Article
id doaj-art-cb5cf48445894ffb93d2e14e15e364c6
institution Kabale University
issn 2045-2322
language English
publishDate 2025-07-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-cb5cf48445894ffb93d2e14e15e364c62025-08-20T03:46:04ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-11993-wThe SARS-CoV-2 main protease causes mitochondrial dysfunction in a yeast modelWojciech Grabiński0Anna Kicińska1Karolina Funtowicz2Tomasz Skrzypczak3Andonis Karachitos4Department of Bioenergetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz UniversityDepartment of Bioenergetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz UniversityDepartment of Bioenergetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz UniversityCenter for Advanced Technology, Adam Mickiewicz UniversityDepartment of Bioenergetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz UniversityAbstract Saccharomyces cerevisiae has proven to be an invaluable model organism for studying mitochondrial function owing to its genetic tractability and the high conservation of mitochondrial processes among eukaryotes, including humans. Yeasts are easy to culture and manipulate genetically, which allows rapid generation of mutant strains and detailed dissection of mitochondrial pathways. In addition, the ability of yeasts to survive without functional mitochondria allows the study of mutations that are lethal to organisms that are dependent on aerobic metabolism. Taking advantage of these benefits, we investigated the toxicity of SARS-CoV-2 main protease (Mpro) expression in yeast under conditions that enforce mitochondria-dependent aerobic metabolism. Our results showed that Mpro expression was highly toxic and significantly impaired yeast growth. Pronounced changes in the morphology and mitochondrial function were observed, indicating that mitochondrial pathways are exceptionally sensitive to Mpro activity. These results provide insights that may be relevant for understanding the effects of Mpro in more complex eukaryotic systems.https://doi.org/10.1038/s41598-025-11993-w
spellingShingle Wojciech Grabiński
Anna Kicińska
Karolina Funtowicz
Tomasz Skrzypczak
Andonis Karachitos
The SARS-CoV-2 main protease causes mitochondrial dysfunction in a yeast model
Scientific Reports
title The SARS-CoV-2 main protease causes mitochondrial dysfunction in a yeast model
title_full The SARS-CoV-2 main protease causes mitochondrial dysfunction in a yeast model
title_fullStr The SARS-CoV-2 main protease causes mitochondrial dysfunction in a yeast model
title_full_unstemmed The SARS-CoV-2 main protease causes mitochondrial dysfunction in a yeast model
title_short The SARS-CoV-2 main protease causes mitochondrial dysfunction in a yeast model
title_sort sars cov 2 main protease causes mitochondrial dysfunction in a yeast model
url https://doi.org/10.1038/s41598-025-11993-w
work_keys_str_mv AT wojciechgrabinski thesarscov2mainproteasecausesmitochondrialdysfunctioninayeastmodel
AT annakicinska thesarscov2mainproteasecausesmitochondrialdysfunctioninayeastmodel
AT karolinafuntowicz thesarscov2mainproteasecausesmitochondrialdysfunctioninayeastmodel
AT tomaszskrzypczak thesarscov2mainproteasecausesmitochondrialdysfunctioninayeastmodel
AT andoniskarachitos thesarscov2mainproteasecausesmitochondrialdysfunctioninayeastmodel
AT wojciechgrabinski sarscov2mainproteasecausesmitochondrialdysfunctioninayeastmodel
AT annakicinska sarscov2mainproteasecausesmitochondrialdysfunctioninayeastmodel
AT karolinafuntowicz sarscov2mainproteasecausesmitochondrialdysfunctioninayeastmodel
AT tomaszskrzypczak sarscov2mainproteasecausesmitochondrialdysfunctioninayeastmodel
AT andoniskarachitos sarscov2mainproteasecausesmitochondrialdysfunctioninayeastmodel