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Bioessays. 2016 Jan;38(1):64-76. doi: 10.1002/bies.201500082. Epub 2015 Dec 12.

Mitochondria and the non-genetic origins of cell-to-cell variability: More is different.

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Department of Condensed Matter Physics, Materials Science Institute 'Nicolás Cabrera' and Institute of Condensed Matter Physics (IFIMAC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.
Centro Nacional de Biotecnología, CSIC, Campus de Cantoblanco, Madrid, Spain.


Gene expression activity is heterogeneous in a population of isogenic cells. Identifying the molecular basis of this variability will improve our understanding of phenomena like tumor resistance to drugs, virus infection, or cell fate choice. The complexity of the molecular steps and machines involved in transcription and translation could introduce sources of randomness at many levels, but a common constraint to most of these processes is its energy dependence. In eukaryotic cells, most of this energy is provided by mitochondria. A clonal population of cells may show a large variability in the number and functionality of mitochondria. Here, we discuss how differences in the mitochondrial content of each cell contribute to heterogeneity in gene products. Changes in the amount of mitochondria can also entail drastic alterations of a cell's gene expression program, which ultimately leads to phenotypic diversity. Also watch the Video Abstract.


alternative splicing; gene expression noise; non-genetic variability; transcription

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