Mitochondrial heterogeneity,metabolic scaling and cell death |
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Authors: | Juvid Aryaman Hanne Hoitzing Joerg P. Burgstaller Iain G. Johnston Nick S. Jones |
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Affiliation: | 1. Department of Mathematics, Imperial College London, London, UK;2. BHF Centre for Research Excellence, National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, London, UK;3. Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, Austria;4. School of Biosciences, University of Birmingham, Birmingham, UK |
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Abstract: | 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. |
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Keywords: | cell death cell size heterogeneity metabolic scaling mitochondria mitochondrial membrane potential |
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