Sunday, 23 October 2016

Cellular Allometry of Mitochondrial Functionality Establishes the Optimal Cell Size

Teemu P. Miettinen and Mikael Björklund

Cells in a population, despite having the same genetic content, are often very different from each other due to the stochastic nature of biological processes. An example is cellular size: some cells are big, some are small and some have an intermediate size. How does the size of a cell affect its functionality? Is there an optimal cell size? This paper focusses on how mitochondrial functionality changes with cell size.

It is known that if a cell is twice as big, it will approximately have twice as many mitochondria, keeping the mitochondrial density roughly constant. However, the expression of mitochondrial genes becomes less than twice as high, meaning that bigger cells express relatively less mitochondrial genes. This may mean that there is a particular cell size corresponding to optimal mitochondrial functionality.

In the paper, they use single cell flow cytometry to measure the size of about 10^5-10^6 cells. Additionally, the mitochondrial membrane potential per unit cell size (ΔΨ) is measured. The relationship between cell size and ΔΨ can then be investigated.

Some of the findings are:
  • Consistent with previous studied, mitochondrial mass increases linearly with cell size
  • ΔΨ first increases as cells get larger, but then decreases again as cells get very large.
  • Mitochondrial respiration is highest in intermediate-sized cells
  • Intermediate-sized cells show the lowest variation in mitochondrial membrane potential
  • A higher ΔΨ variation is correlated with a higher rate of apoptosis (cell death)
  • Intermediate-sized cells showed (on average) the fastest growth

These results strongly indicate that mitochondrial functionality is largest in intermediate-sized cells in a population. Cells also seem to try to maintain the size at which mitochondrial functionality is largest, meaning that this is probably an optimal cell size.

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