Mitochondrial heterogeneity, metabolic scaling and cell death.

Juvid Aryaman,Hanne Hoitzing,Iain G Johnston,Nick S Jones,Joerg P Burgstaller

doi:10.1002/bies.201700001

Juvid Aryaman, Hanne Hoitzing + Show 3 more

Open Access

https://doi.org/10.1002/bies.201700001

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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.

Highlights

Non-genetic heterogeneity describes observable differences between genetically identical cells, and is a fundamental observation in cell biology [1,2,3], with implications for important biological phenomena including development [4, 5], bacterial persistence [6], cancer malignancy and drug resistance [7]
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 Keywords: cell death; cell size; heterogeneity; metabolic scaling; mitochondria; mitochondrial membrane potential
A bioenergetic proposal: A combination of scaling of cellular power demand with cell size, and cell death, may account for observed patterns of mitochondrial functionality In Box 2, we propose that metabolic scaling with a particular model of cell death may recover the turning behaviour in relate mitochondrial functionality (rDC) with cell radius observed by Miettinen and Bjo€rklund [26]