Mitochondria is a very tiny structure present in most cells, are identified for their energy-generating machinery. Now, Salk researchers have found a new function of mitochondria; they set off molecular alarms when cells are exposed to chemicals or stress that may damage DNA, such as chemotherapy. The results revealed online in Nature Metabolism on December 9, 2019, may result in new cancer treatments that stop tumors from becoming immune to chemotherapy.
A lot of the DNA that a cell must function is discovered inside the cell’s nucleus, inherited from both parents, packaged in chromosomes. However, mitochondria, everyone includes their very own small circles of DNA (known as mitochondrial DNA, passed only from a mother to her offspring. And most cells include thousands—and even thousands—of mitochondria.
Within the new research, Shadel and his colleagues set out to look in additional elements when molecular pathways are activated by the release of damaged mitochondrial DNA into the cell’s inside. They homed in on a subset of genes, often known as interferon-stimulated genes, or ISGs, which can be usually activated by the presence of viruses. However, in this case, the group realized, the genes have been a specific subset of ISGs turned on by viruses. And this similar subset of ISGs is usually discovered to be activated in cancer cells, which has developed resistance to chemotherapy with DNA-damaging agents like doxyrubicin.
To destroy cancer, doxyrubicin targets nuclear DNA. However, the new research discovered that the drug additionally causes the damage and release of mtDNA, which in turn, activates ISGs. This subset of ISGs, the group found, helps protect nuclear DNA from damage—and, thus, causes increased resistance to the chemotherapy drug.