Aryaman Juvid, Hoitzing Hanne, Burgstaller Joerg P, Johnston Iain G, Jones Nick S
Department of Mathematics, Imperial College London, London, UK.
BHF Centre for Research Excellence, National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, London, UK.
Bioessays. 2017 Jul;39(7). doi: 10.1002/bies.201700001. Epub 2017 Jun 8.
Heterogeneity in mitochondrial content has been previously suggested as a major contributor to cellular noise, with multiple studies indicating its direct involvement in biomedically important cellular phenomena. A recently published dataset explored the connection between mitochondrial functionality and cell physiology, where a non-linearity between mitochondrial functionality and cell size was found. Using mathematical models, we suggest that a combination of metabolic scaling and a simple model of cell death may account for these observations. However, our findings also suggest the existence of alternative competing hypotheses, such as a non-linearity between cell death and cell size. While we find that the proposed non-linear coupling between mitochondrial functionality and cell size provides a compelling alternative to previous attempts to link mitochondrial heterogeneity and cell physiology, we emphasise the need to account for alternative causal variables, including cell cycle, size, mitochondrial density and death, in future studies of mitochondrial physiology.
线粒体含量的异质性先前已被认为是细胞噪声的主要成因，多项研究表明其直接参与了具有重要生物医学意义的细胞现象。最近发布的一个数据集探究了线粒体功能与细胞生理学之间的联系，结果发现线粒体功能与细胞大小之间存在非线性关系。通过数学模型，我们认为代谢标度和一个简单的细胞死亡模型相结合或许可以解释这些观察结果。然而，我们的研究结果也表明存在其他相互竞争的假说，比如细胞死亡与细胞大小之间的非线性关系。虽然我们发现所提出的线粒体功能与细胞大小之间的非线性耦合为之前将线粒体异质性与细胞生理学联系起来的尝试提供了一个有说服力的替代解释，但我们强调在未来线粒体生理学研究中需要考虑其他因果变量，包括细胞周期、大小、线粒体密度和死亡。
