Effects of bursty synthesis in organelle biogenesis

IF 1.9 4区 数学 Q2 BIOLOGY Mathematical Biosciences Pub Date : 2024-02-10 DOI:10.1016/j.mbs.2024.109156
Binayak Banerjee, Dipjyoti Das
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Abstract

A fundamental question of cell biology is how cells control the number of organelles. The processes of organelle biogenesis, namely de novo synthesis, fission, fusion, and decay, are inherently stochastic, producing cell-to-cell variability in organelle abundance. In addition, experiments suggest that the synthesis of some organelles can be bursty. We thus ask how bursty synthesis impacts intracellular organelle number distribution. We develop an organelle biogenesis model with bursty de novo synthesis by considering geometrically distributed burst sizes. We analytically solve the model in biologically relevant limits and provide exact expressions for the steady-state organelle number distributions and their means and variances. We also present approximate solutions for the whole model, complementing with exact stochastic simulations. We show that bursts generally increase the noise in organelle numbers, producing distinct signatures in noise profiles depending on different mechanisms of organelle biogenesis. We also find different shapes of organelle number distributions, including bimodal distributions in some parameter regimes. Notably, bursty synthesis broadens the parameter regime of observing bimodality compared to the ‘non-bursty’ case. Together, our framework utilizes number fluctuations to elucidate the role of bursty synthesis in producing organelle number heterogeneity in cells.

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细胞器生物发生过程中猝灭合成的影响
细胞生物学的一个基本问题是细胞如何控制细胞器的数量。细胞器的生物发生过程,即从头合成、裂变、融合和衰变,本身就具有随机性,从而导致细胞间细胞器丰度的变化。此外,实验表明,某些细胞器的合成可能是突发性的。因此,我们提出了突发性合成如何影响细胞内细胞器数量分布的问题。通过考虑几何分布的猝发大小,我们建立了一个具有猝发从头合成的细胞器生物发生模型。我们对该模型进行了生物相关极限的分析求解,并给出了稳态细胞器数量分布及其均值和方差的精确表达式。我们还提出了整个模型的近似解,并辅以精确的随机模拟。我们发现,猝发通常会增加细胞器数量的噪声,并根据细胞器生物生成的不同机制产生不同的噪声特征。我们还发现细胞器数量分布的不同形状,包括某些参数区的双峰分布。值得注意的是,与 "非突发性 "情况相比,突发性合成扩大了观察双峰分布的参数范围。总之,我们的框架利用数量波动来阐明猝发合成在细胞中产生细胞器数量异质性的作用。
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来源期刊
Mathematical Biosciences
Mathematical Biosciences 生物-生物学
CiteScore
7.50
自引率
2.30%
发文量
67
审稿时长
18 days
期刊介绍: Mathematical Biosciences publishes work providing new concepts or new understanding of biological systems using mathematical models, or methodological articles likely to find application to multiple biological systems. Papers are expected to present a major research finding of broad significance for the biological sciences, or mathematical biology. Mathematical Biosciences welcomes original research articles, letters, reviews and perspectives.
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