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Published on: June 14, 2013
Regulation of yeast oscillatory dynamics
Douglas B Murray1, Manfred Beckmann, Hiroaki Kitano
1ERATO-SORST Kitano Symbiotic Systems Project, Japan Science and Technology Agency, 9S3 Shinanomachi Research Park, Keio University School of Medicine, 35 Shinanomachi, Tokyo 160-8582, Japan. dougie@symbio.jst.go.jp
Yeast cells exhibit respiratory oscillations, a phenomenon where metabolic and transcriptional events are tightly regulated. This study reveals a heterarchical control system involving coupled networks of proteins and metabolites, rather than a strict hierarchy.
Area of Science:
- Cellular Biology
- Systems Biology
- Biochemistry
Background:
- High cell density continuous yeast culture induces population-wide respiratory oscillations.
- Temporal separation of cellular functions occurs during these oscillations, but regulatory mechanisms are unclear.
Purpose of the Study:
- To elucidate the regulatory mechanisms governing respiratory oscillations in yeast.
- To identify key components and control strategies involved in cellular timing circuits.
Main Methods:
- Gas chromatography-mass spectrometry (GC-MS) for metabolite analysis.
- Microarray data analysis for transcriptional profiling.
- Statistical analysis of transcription factor activity.
- Network analysis of yeast interaction data.
- Controlled experimental perturbations.
Main Results:
- The majority of metabolites (70%) displayed oscillatory dynamics, peaking with nicotinamide adenine dinucleotide (phosphate) (NAD(P)H).
- Biosynthetic events follow a defined temporal order, initiated by increasing respiration rates.
- A transcriptional complex was identified as part of the timing circuit for biosynthetic, reductive, and cell cycle programs.
- Oscillatory regulation involves coupled subgraphs of proteins and metabolites with heterarchical control.
Conclusions:
- Respiratory oscillations in yeast are regulated by complex, coupled networks without a clear hierarchy.
- Both metabolic and transcriptional data support a heterarchical model for cellular timing and regulation.
- Translational, proteomic, and metabolic mechanisms interact to maintain oscillatory dynamics.
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