In:
eLife, eLife Sciences Publications, Ltd, Vol. 3 ( 2014-10-01)
Abstract:
The DNA in a cell's nucleus must be copied faithfully, and divided equally, when a cell divides to produce two new cells. Mistakes—or mutations—are sometimes made during the copying process, and mutations can also be introduced by exposing DNA to damaging agents known as mutagens, such as UV light or cigarette smoke. These mutations are then maintained in all of the descendants of the cell. Most of these mutations have no impact on the cell's characteristics (‘passenger mutations’). However, ‘driver mutations’ that allow cells to divide uncontrollably and spread to other body sites can lead to cancer. Mitochondria are cellular compartments that are responsible for generating the energy a cell needs to survive and are also responsible for initiating programmed cell death. Mitochondria contain their own DNA—entirely separate from that in the nucleus of the cell—that encodes the proteins most essential for energy production. Mitochondrial DNA molecules are frequently exposed to damaging molecules called reactive oxygen species that are produced by the mitochondria. Therefore, these reactive oxygen species have been thought to be one of the most important causes of mitochondrial DNA mutations. In addition, because cancer cells produce energy differently to normal cells, mutations in the mitochondrial DNA that change the ability of the mitochondria to produce energy have been conventionally thought to help normal cells to become cancerous. However, conclusive evidence for a link between cancer and mitochondrial DNA mutations is lacking. Ju et al. examined the mitochondrial DNA sequences taken from 1675 cancer biopsies from over thirty different types of cancer and compared these to normal tissue from the same patients. This revealed 1907 mutations in the mitochondrial DNA taken from the cancer cells. The pattern of the mutations suggests that the majority of the mutations are not introduced from reactive oxygen species, but from the errors the mitochondria themselves make in the process of duplicating their DNA when a cell divides. Unexpectedly, known mutagens, such as cigarette smoke or UV light, had a negligible effect on mitochondrial DNA mutations. Contrary to conventional wisdom, Ju et al. found no evidence that the mitochondrial DNA mutations help cancer to develop or spread. Instead, like passenger mutations found in the DNA in the cell nucleus, most mitochondrial genome mutations have no discernible effect. However, Ju et al. revealed that DNA mutations that damage normal mitochondrial activity are less likely to be maintained in cancer cells. Presumably, mitochondria containing these proteins produce less energy, and so a cell containing too many of these mutations will find it harder to survive. This shows that having enough correctly functioning mitochondria is essential for even cancer cells to thrive.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.02935.001
DOI:
10.7554/eLife.02935.002
DOI:
10.7554/eLife.02935.003
DOI:
10.7554/eLife.02935.004
DOI:
10.7554/eLife.02935.005
DOI:
10.7554/eLife.02935.006
DOI:
10.7554/eLife.02935.007
DOI:
10.7554/eLife.02935.008
DOI:
10.7554/eLife.02935.009
DOI:
10.7554/eLife.02935.010
DOI:
10.7554/eLife.02935.011
DOI:
10.7554/eLife.02935.012
DOI:
10.7554/eLife.02935.013
DOI:
10.7554/eLife.02935.014
DOI:
10.7554/eLife.02935.015
DOI:
10.7554/eLife.02935.016
DOI:
10.7554/eLife.02935.017
DOI:
10.7554/eLife.02935.018
DOI:
10.7554/eLife.02935.019
DOI:
10.7554/eLife.02935.020
DOI:
10.7554/eLife.02935.021
DOI:
10.7554/eLife.02935.022
DOI:
10.7554/eLife.02935.023
DOI:
10.7554/eLife.02935.024
DOI:
10.7554/eLife.02935.025
DOI:
10.7554/eLife.02935.026
DOI:
10.7554/eLife.02935.027
DOI:
10.7554/eLife.02935.028
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2014
detail.hit.zdb_id:
2687154-3
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