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bioRxiv · 10.64898/2026.03.30.715437

Competition between mitochondrial and cytosolic ribosomes produces a bistable metabolic switch

Nanda, P.·Murray, A. W.
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Abstract

We investigated the molecular basis of bet-hedging in budding yeast, Saccharomyces cerevisiae. Fast glycolytic growth generates two cell states: fermenting arrestors and respiring recoverers, of which only recoverers resume growth when shifted to a respiratory carbon source. Single-cell metabolic biosensors show that a bistable switch in mitochondrial activity produces these states: mitochondrial membrane potential drives import of positively charged, nuclear-encoded proteins of the mitochondrial ribosome, and mitochondrial ribosomes synthesize electron transport chain subunits that sustain the potential, completing a positive feedback loop. The ratio of mitochondrial to cytoplasmic protein synthesis governs switch dynamics: the effect of slowing mitochondrial translation is rescued by inhibiting cytosolic translation. Reducing mitochondrial translation reconstitutes bistability in evolutionarily distant fission yeast, suggesting a conserved mechanism for diversifying single-cell ATP production strategies.

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Nanda, P., Murray, A. W.. 2026-03-31. Competition between mitochondrial and cytosolic ribosomes produces a bistable metabolic switch. https://doi.org/10.64898/2026.03.30.715437

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