Minute-scale proteomics profiling resolves the chronological mechanics of yeast cell death
摘要
Biological state transitions operate as continuous processes, yet are predominantly studied through discrete snapshots that obscure longitudinal dynamics. To resolve this, we monitored the proteome dynamics of Saccharomyces cerevisiae under lethal stress at 1-minute intervals, generating a minute-scale proteome movie whose high-temporal-resolution protein trajectories reconciled conflicting previous endpoint results by revealing sampling-time-dependent regulatory direction. Using neural ordinary differential equations and time-resolved pathway analysis, we reconstructed the proteome dynamics and identified temporally related molecular events. Acetic acid induced metabolic exhaustion through energy-expensive defense and lethal mitochondrial hyperactivation. Conversely, hydrogen peroxide triggered genomic triage, prioritizing DNA repair at the cost of organelle quality control. Interestingly, longitudinal survival validation suggests that peak autophagy coincides with the loss of reproductive viability, consistent with a late attempt to maintain immediate metabolic persistence that fails to restore cell division. Together, we characterize cell death as a set of temporally orchestrated execution programs, revealing temporal logic from adaptation to irreversible collapse. Ultimately, this study indicates that high-throughput mass spectrometry-based proteomics can construct high-resolution proteome videos, offering a new approach for resolving continuous biological state transitions.
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