Our researchers are authors of a paper on the evolution of a mechanism regulating yeast metabolism

12 02 2026

Scientists from the Institute of Genetics and Biotechnology, with a leading contribution from Dr Karolina Łabędzka-Dmoch and Prof. Paweł Golik, have published research results on the evolution of a mechanism that helps yeasts adapt their metabolism to disturbances in mitochondrial function. The paper titled “Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts” was published in the journal Molecular Biology and Evolution.

Eukaryotic cells arose billions of years ago thanks to a symbiosis of simpler prokaryotic cells – an archaeon and a bacterium. A legacy of this history is the presence of two separate genomes – the main nuclear genome and a reduced mitochondrial genome, which is still necessary to ensure the functions of cellular respiration. The nucleus controls mitochondria because it encodes almost all proteins needed to maintain and operate the mitochondrial genome. In turn, adjusting the expression of the nuclear genome to the physiological state of mitochondria is possible thanks to a signaling pathway called retrograde regulation. This pathway was first described in the yeast S. cerevisiae. A key role in it is played by Rtg transcription factors, which activate target genes and help the cell adapt to reduced mitochondrial activity.

The starting point of the study was to examine the role of Rtg proteins in the yeast Candida albicans – a well-known opportunistic pathogen (also of humans), evolutionarily distant from S. cerevisiae by hundreds of millions of years. The scientists used the ChIP-seq technique, which, using next-generation sequencing, allows identification of places in the genome bound by proteins. It turned out that in C. albicans, Rtg proteins are responsible for the response to defects in mitochondrial function, but they do so by activating a completely different set of genes than their counterparts in S. cerevisiae. These include genes encoding proteins involved in alternative respiration pathways (the so-called alternative oxidase), the response to stress related to the accumulation of reactive oxygen species, and mitophagy – an intracellular “recycling” of improperly functioning mitochondria.

These differences reflect different evolutionary adaptations in various yeast lineages, such as a preference for fermentation (as in S. cerevisiae) or respiration (as in C. albicans), the presence of respiratory complex I in mitochondria (which is absent in S. cerevisiae and its relatives), and pathogenicity. An analysis of genome sequences from more than 1,000 different yeast species showed that the history of retrograde regulation began about 235 million years ago with the duplication of one gene in the ancestor of such different yeasts as Saccharomyces and Candida. The history of the target genes of this pathway, such as the gene encoding alternative oxidase, was much more complex – these genes were repeatedly duplicated or lost in different yeast lineages in response to natural selection pressure during adaptation to different metabolic strategies.

The evolution of the retrograde regulation pathway is a fascinating example of how genes and proteins adapt to perform different functions. Moreover, understanding it may help explain mechanisms important for the pathogenicity of C. albicans and, therefore, support efforts to fight infections caused by these yeasts.

We warmly congratulate the authors of the publication!
The article is available at: https://doi.org/10.1093/molbev/msag005