Unveiling the role of yeast cytochrome c isoforms in the assembly of mitochondrial supercomplexes and the control of respiratory chain rate

Abstract

Mitochondria play crucial roles as both the powerhouse and signaling center of cells, balancing cell survival and death to maintain homeostasis. Disruption of this balance can lead to various diseases. Therefore, exploring the components involved in mitochondrial metabolism presents a significant challenge. In this context, respiratory supercomplexes are evolutionarily conserved, stable associations between membrane complexes and molecules, including proteins and lipids, within the inner mitochondrial membrane. These supercomplexes dynamically respond to metabolic demands, enhancing the electron transfer rate and reducing the production of reactive oxygen species. Recent research has identified cytochrome c, a mobile electron carrier between complexes III and IV, as a potential key player in the formation of these supercomplexes. This study focuses on elucidating the role of cytochrome c in modulating the assembly of supercomplexes, using the yeast Saccharomyces cerevisiae as a model system for mitochondrial metabolism. Our findings indicate that the viability of Saccharomyces cerevisiae relies on the presence of cytochrome c, with both isoforms playing a role in the assembly of respiratory supercomplexes. Notably, isoform-2 of cytochrome c enhances electron transfer efficiency, resulting in reduced ROS production.