Logic of the Yeast Metabolic Cycle: Temporal Compartmentalization of Cellular Processes

Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, L3.124, Dallas, TX 75390, USA.
Science (Impact Factor: 33.61). 12/2005; 310(5751):1152-8. DOI: 10.1126/science.1120499
Source: PubMed


Budding yeast grown under continuous, nutrient-limited conditions exhibit robust, highly periodic cycles in the form of respiratory bursts. Microarray studies reveal that over half of the yeast genome is expressed periodically during these metabolic cycles. Genes encoding proteins having a common function exhibit similar temporal expression patterns, and genes specifying functions associated with energy and metabolism tend to be expressed with exceptionally robust periodicity. Essential cellular and metabolic events occur in synchrony with the metabolic cycle, demonstrating that key processes in a simple eukaryotic cell are compartmentalized in time.

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Available from: Andrzej Kudlicki, Jan 22, 2014
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    • "In contrast, there are a variety of time-dependent (non-steady) processes in cellular metabolism, such as those observed in the cell cycle [24] [25], cyclic AMP signaling [26], circadian rhythms [27] [28] glycolytic oscillation [29] [30] [31] [32] [33] [34] [35] [36], and yeast metabolic cycle (YMC) [37] [38] [39] [40] [41]. The enzyme concentrations change in time during these dynamic processes, which then alters the time scale of the reaction processes, as mentioned above. "
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    ABSTRACT: Cells generally convert nutrient resources to useful products via energy transduction. Accordingly, the thermodynamic efficiency of this conversion process is one of the most essential characteristics of living organisms. However, although these processes occur under conditions of dynamic metabolism, most studies of cellular thermodynamic efficiency have been restricted to examining steady states; thus, the relevance of dynamics to this efficiency has not yet been elucidated. Here, we develop a simple model of metabolic reactions with anabolism-catabolism coupling catalysed by enzymes. Through application of external oscillation in the enzyme abundances, the thermodynamic efficiency of metabolism was found to be improved. This result is in strong contrast with that observed in the oscillatory input, in which the efficiency always decreased with oscillation. This improvement was effectively achieved by separating the anabolic and catabolic reactions, which tend to disequilibrate each other, and taking advantage of the temporal oscillations so that each of the antagonistic reactions could progress near equilibrium. In this case, anti-phase oscillation between the reaction flux and chemical affinity through oscillation of enzyme abundances is essential. This improvement was also confirmed in a model capable of generating autonomous oscillations in enzyme abundances. Finally, the possible relevance of the improvement in thermodynamic efficiency is discussed with respect to the potential for manipulation of metabolic oscillations in microorganisms.
    • "The function in regulation of mitochondrial oxidative metabolism is well conserved in a C. elegans Bmal1- like protein, AHA-1, which also modulates longevity. Of note, a metabolic cycle (occurring in 4 to 5 hr) has been described in yeast under a constant low-glucose culture condition (Tu et al., 2005), in which a reductive, nonrespiratory phase is followed by an oxidative, respiratory phase with increased oxygen consumption . This rhythmic respiration is facilitated by temporal expression of mitochondrial OXPHOS genes, suggesting the compartmentalization of mitochondrial oxidative metabolism in time is evolutionarily advantageous to optimize metabolic output (Tu and McKnight, 2007). "
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    ABSTRACT: Mitochondria undergo architectural/functional changes in response to metabolic inputs. How this process is regulated in physiological feeding/fasting states remains unclear. Here we show that mitochondrial dynamics (notably fission and mitophagy) and biogenesis are transcriptional targets of the circadian regulator Bmal1 in mouse liver and exhibit a metabolic rhythm in sync with diurnal bioenergetic demands. Bmal1 loss-of-function causes swollen mitochondria incapable of adapting to different nutrient conditions accompanied by diminished respiration and elevated oxidative stress. Consequently, liver-specific Bmal1 knockout (LBmal1KO) mice accumulate oxidative damage and develop hepatic insulin resistance. Restoration of hepatic Bmal1 activities in high-fat-fed mice improves metabolic outcomes, whereas expression of Fis1, a fission protein that promotes quality control, rescues morphological/metabolic defects of LBmal1KO mitochondria. Interestingly, Bmal1 homolog AHA-1 in C. elegans retains the ability to modulate oxidative metabolism and lifespan despite lacking circadian regulation. These results suggest clock genes are evolutionarily conserved energetics regulators.
    Cell metabolism 09/2015; 22(4). DOI:10.1016/j.cmet.2015.08.006 · 17.57 Impact Factor
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    • ". NF-APIN (Xiao et al., 2013), APPIN (Wang et al., 2013), TC-PIN (Tang et al., 2011), TSN-PCD (Li et al., 2012) and PCD-GED methods comparison (considering their best parameter values) based on DIP(Xenarios, Salwinski et al., 2002), PPI network and GED1 (Tu, Kudlicki et al., 2005), gene expression data. Best parameters settings for PCD- GED are α ¼0.8, β ¼0.3. "
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