Mukherji Shankar, O'Shea Erin K
FAS Center for Systems Biology, Harvard University, Cambridge, United States Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States Howard Hughes Medical Institute, Harvard University, Cambridge, United States.
FAS Center for Systems Biology, Harvard University, Cambridge, United States Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States Howard Hughes Medical Institute, Harvard University, Cambridge, United States Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
Elife. 2014 Jun 10;3:e02678. doi: 10.7554/eLife.02678.
Fluctuations in organelle abundance can profoundly limit the precision of cell biological processes from secretion to metabolism. We modeled the dynamics of organelle biogenesis and predicted that organelle abundance fluctuations depend strongly on the specific mechanisms that increase or decrease the number of a given organelle. Our model exactly predicts the size of experimentally measured Golgi apparatus and vacuole abundance fluctuations, suggesting that cells tolerate the maximum level of variability generated by the Golgi and vacuole biogenesis pathways. We observe large increases in peroxisome abundance fluctuations when cells are transferred from glucose-rich to fatty acid-rich environments. These increased fluctuations are significantly diminished in mutants lacking peroxisome fission factors, leading us to infer that peroxisome biogenesis switches from de novo synthesis to primarily fission. Our work provides a general framework for exploring stochastic organelle biogenesis and using fluctuations to quantitatively unravel the biophysical pathways that control the abundance of subcellular structures.DOI: http://dx.doi.org/10.7554/eLife.02678.001.
细胞器丰度的波动会严重限制从分泌到代谢等细胞生物学过程的精确性。我们对细胞器生物发生的动力学进行了建模,并预测细胞器丰度的波动在很大程度上取决于增加或减少特定细胞器数量的具体机制。我们的模型准确预测了实验测量的高尔基体和液泡丰度波动的大小,这表明细胞能够容忍由高尔基体和液泡生物发生途径产生的最大变异性水平。当细胞从富含葡萄糖的环境转移到富含脂肪酸的环境时,我们观察到过氧化物酶体丰度波动大幅增加。在缺乏过氧化物酶体分裂因子的突变体中,这些增加的波动显著减小,这使我们推断过氧化物酶体生物发生从从头合成转变为主要通过分裂进行。我们的工作为探索随机细胞器生物发生以及利用波动来定量解析控制亚细胞结构丰度的生物物理途径提供了一个通用框架。DOI: http://dx.doi.org/10.7554/eLife.02678.001