Friday 1 July 2011

Power and genes: effects of mitochondrial variability

Cells make stuff and they need power to do this. But what would happen if their power stations were as variable as wind power? Presumably you'd expect that, for cells with a lower average supply of power, they would make stuff (e.g. proteins and protein precursors called RNA transcripts) more slowly and take longer to go forth and multiply (move through their cell cycle). Since you'd imagine that these consequences of power supply variability would be as disadvantageous for the cell as power-cuts for us, I would have guessed that this kind of variability in power would be tightly controlled by the cell. Seems maybe not.

Francisco Iborra now at the Centro Nacional de Biotecnologica in Madrid came to me with some startling data that he had been producing, along with his student Ricardo Neves (now at Biocant in Portugal) and others at the Weatherall Institute for Molecular Medicine. It suggested that maybe cells do show a form of marked power variability: some cells appear to be making gene products faster than others (the picture shows variability in the rate at which gene transcripts are made between cells - each cell's nucleus is the circular blob) and this is related to measures of their mitochondrial content (the number of power stations they have). The cells with more mitochondria at birth also appear to divide sooner than more disadvantaged siblings. The paper "Connecting Variability in Global Transcription Rate to Mitochondrial Variability" can be found on our papers page and appeared in PLoS Biology. Becky Ward it takes 30 - was nice enough to blog interestingly about it (she's worth following).

This might seem like a curiosity, but the fact that some cells differ from others can be very important. While we tailor our treatments of sets of cells, like cancers, to typical cells - maybe cells which, by chance, are very atypical (e.g. lazy and power limited) will respond in a very different way. You only need a few such unusual cells to survive your treatment and they'll repopulate your cancer. In fact the study of cellular variability and its origins is now a major field driven by fun researchers like t h e s e. It's still not very clear why two genes in the same organism might co-vary in the levels of their gene products (called extrinsic noise) and our paper makes an experimental contribution to this: we've just finished a paper which combines a mathematical model plus some more experiments to help illuminate our findings further. Nick

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