The two yeast cytochrome c isoforms differentially regulate supercomplex assembly and mitochondrial electron flow
Mitochondria play a crucial role in cellular energy production, signaling and homeostasis. Respiratory supercomplexes represent evolutionary well-conserved, stable associations between membrane complexes and molecules, including proteins and lipids, within the inner mitochondrial membrane. They dyna...
| Autores: | , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Recursos: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/173018 |
| Acesso em linha: | https://hdl.handle.net/11441/173018 https://doi.org/10.1016/j.ijbiomac.2025.144143 |
| Access Level: | acceso abierto |
| Palavra-chave: | Cytochrome c Electron transport chain Mitochondria Respiratory supercomplexes Saccharomyces cerevisiae |
| Resumo: | Mitochondria play a crucial role in cellular energy production, signaling and homeostasis. Respiratory supercomplexes represent evolutionary well-conserved, stable associations between membrane complexes and molecules, including proteins and lipids, within the inner mitochondrial membrane. They dynamically respond to metabolic demands and enhance the electron transfer rate, thereby reducing the production of ROS. Recent research has unveiled cytochrome c, a mobile electron carrier between complexes III and IV, as a potential key player in orchestrating the formation of these supra-associations. This study centers on elucidating the role of cytochrome c in modulating the assembly of supercomplexes, using the Saccharomyces cerevisiae yeast as a model system for mitochondrial metabolism. BN-PAGE and mass spectrometry-based proteomic analysis were employed to examine supercomplex organization in yeast strains expressing different cytochrome c isoforms, grown under fermentative and respiratory conditions. Our results demonstrate that both isoforms of cytochrome c contribute to supercomplex assembly, with isoform-2 significantly improving electron transfer and lowering ROS levels. We propose a model in which cytochrome c acts as a scaffold for the recruitment of assembly factors, facilitating the formation of higher order supercomplexes such as III2IV2. This model highlights cytochrome c's role beyond electron transfer, as it regulates supercomplex assembly and mitochondrial homeostasis. |
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