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No support for cell size as a driver of tissue-level metabolic rates at the upper limits of animal cell size

Itgen, M. W.; Chicco, A. J.; Mueller, R. L.

2026-06-18 evolutionary biology
10.64898/2026.06.17.733039 bioRxiv
Show abstract

Evolutionary diversity in metabolic rate underlies differences in physiology, morphology, and life history across the tree of life. Cell size has been proposed as an important determinant of metabolic rate. The mechanisms underlying this proposed connection are based on the lower surface area to volume ratios in larger cells. As relative surface area decreases, the cost of maintaining ion gradients across the cell membrane through action of the Na+/K+-ATPase pump are posited to decrease, lowering overall metabolic costs. Despite strong theoretical support for this model, and its incorporation into broader models of life history evolution, empirical measurement of Na+/K+-ATPase activity in species that differ in cell size has been lacking. Here, we study nine species of salamanders of the genus Plethodon that span a large range of cell sizes approaching the animal upper limit. We compare basal cellular respiration rates, relative cost of the Na+/K+-ATPase pump, and maximal mitochondrial respiration rates in liver and heart tissue. Contrary to predictions, we find no support for a relationship between cell size and any of these mitochondrial respiratory variables. We reconcile this surprising result with broader phylogenetic studies showing a lack of correlation between cell size and metabolic rate at the organismal level.

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