Mairet, F. | Search bioRxiv

bioRxiv2026

Mitochondrial ribosome content as a proxy for respiration

Quantifying cellular activities remains a major challenge across fields ranging from microbial ecology to biotechnology and biomedical sciences. Building on the well-established linear relationship between growth rate and ribosome content -- the so-called microbial growth law -- this study proposes using organelle ribosome content to infer metabolic activity. In exponentially growing yeast, including under overflow conditions, a strong linear correlation was observed between mitochondrial ribosome content and oxygen uptake rate, demonstrating the robustness and potential of this approach. In addition, cytoplasmic and mitochondrial ribosome fractions exhibited a linear relationship, while overflow conditions appeared as outliers, providing a means to identify such metabolic states. Altogether, these findings highlight the promise of organelle ribosome quantification as a novel proxy for deciphering cellular metabolism.

systems biology↗

bioRxiv2023

In silico identification of switching nodes in metabolic networks

AO_SCPLOWBSTRACTC_SCPLOWCells modulate their metabolism according to environmental conditions. A major challenge to better understand metabolic regulation is to identify, from the hundreds or thousands of molecules, the key metabolites where the re-orientation of fluxes occurs. Here, a method called ISIS (for In Silico Identification of Switches) is proposed to locate these nodes in a metabolic network, based on the analysis of a set of flux vectors (obtained e.g. by parsimonious flux balance analysis with different inputs). A metabolite is considered as a switch if the fluxes at this point are redirected in a different way when conditions change. The soundness of ISIS is shown with four case studies, using both core and genome-scale metabolic networks of Escherichia coli, Saccharomyces cerevisiae and the diatom Phaeodactylum tricornutum. Through these examples, we show that ISIS can identify hot-spots where fluxes are reoriented. Additionally, switch metabolites are deeply involved in post-translational modification of proteins, showing their importance in cellular regulation. In P. tricornutum, we show that Erythrose 4-phosphate is an important switch metabolite for mixotrophy suggesting the importance of this metabolite in the non-oxidative pentose phosphate pathway to orchestrate the flux variations between glycolysis, the Calvin cycle and the oxidative pentose phosphate pathway when the trophic mode changes. Finally, a comparison between ISIS and reporter metabolites identified with transcriptomic data confirms the key role of metabolites such as L-glutamate or L-aspartate in the yeast response to nitrogen input variation. Overall, ISIS opens up new possibilities for studying cellular metabolism and regulation, as well as potentially for developing metabolic engineering.

systems biology↗