Scaling of biosynthesis and metabolism with cell size

Abstract

Cells adopt a size that is optimal for their function, and pushing them beyond this limit can cause cell aging and death by senescence or reduce proliferative potential. However, by increasing their genome copy number (ploidy), cells can increase their size dramatically and homeostatically maintain physiological properties such as biosynthesis rate. Recent studies investigating the relationship between cell size and rates of biosynthesis and metabolism under normal, polyploid, and pathological conditions are revealing new insights into how cells attain the best function or fitness for their size by tuning processes including transcription, translation, and mitochondrial respiration. A new frontier is to connect single-cell scaling relationships with tissue and whole-organism physiology, which promises to reveal molecular and evolutionary principles underlying the astonishing diversity of size observed across the tree of life.

FIGURE 1:

Examples of biosynthesis and metabolism scaling with cell size. (a) In budding yeast, mRNA and protein levels scale with cell size. The upper limit to a physiologically fit size range is thought to be set by ploidy, which can become rate-limiting for transcription. (b) Cellular respiration and metabolic rate appear to decrease with cell size. (i) In immortalized human cells, mitochondrial efficiency is optimal at intermediate cell sizes (Miettinen and Bjorklund, 2016). (ii) In human stem cells, mitochondrial- and nuclear-encoded oxidative phosphorylation genes are expressed at higher levels in haploids compared with diploids (Sagi et al., 2016). (iii) Across unicellular organisms, a power law with an exponent <1 relates cellular metabolic rate and cell size (Glazier, 2009).