Methionine supplementation stimulates mitochondrial respiration |
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Authors: | Farida Tripodi Andrea Castoldi Raffaele Nicastro Veronica Reghellin Linda Lombardi Cristina Airoldi Ermelinda Falletta Elisa Maffioli Pasquale Scarcia Luigi Palmieri Lilia Alberghina Gennaro Agrimi Gabriella Tedeschi Paola Coccetti |
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Institution: | 1. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy;2. SYSBIO, Centre of Systems Biology, Milan, Italy;3. Department of Chemistry, University of Milano, Milan, Italy;4. DIMEVET – Department of Veterinary Medicine, University of Milano, Milan, Italy;5. Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Italy |
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Abstract: | Mitochondria play essential metabolic functions in eukaryotes. Although their major role is the generation of energy in the form of ATP, they are also involved in maintenance of cellular redox state, conversion and biosynthesis of metabolites and signal transduction. Most mitochondrial functions are conserved in eukaryotic systems and mitochondrial dysfunctions trigger several human diseases.By using multi-omics approach, we investigate the effect of methionine supplementation on yeast cellular metabolism, considering its role in the regulation of key cellular processes. Methionine supplementation induces an up-regulation of proteins related to mitochondrial functions such as TCA cycle, electron transport chain and respiration, combined with an enhancement of mitochondrial pyruvate uptake and TCA cycle activity. This metabolic signature is more noticeable in cells lacking Snf1/AMPK, the conserved signalling regulator of energy homeostasis. Remarkably, snf1Δ cells strongly depend on mitochondrial respiration and suppression of pyruvate transport is detrimental for this mutant in methionine condition, indicating that respiration mostly relies on pyruvate flux into mitochondrial pathways.These data provide new insights into the regulation of mitochondrial metabolism and extends our understanding on the role of methionine in regulating energy signalling pathways. |
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Keywords: | Snf1/AMPK Metabolomics Shotgun proteomics MPC (mitochondrial pyruvate carrier) a |
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