Our bodies constantly encounter oxidants from our diet and metabolism. Oxidative stress is thought to speed up ageing, and increase the risk of diseases like cancer or dementia. However, there have been few clues to how oxidative stress can cause these problems, or how anti-oxidants may work to combat them. Now, Professor Ashok Venkitaraman’s laboratory has discovered a way in which oxidative stress damages mitochondria – the powerhouses that supply energy to our cells. His team found that oxidative stress blocks mitochondria from duplicating and renewing themselves, by creating lesions in mitochondrial DNA that prevent the DNA-copying machinery from working correctly.

Prof. Venkitaraman’s lab discovered this new link between oxidative stress and mitochondrial DNA renewal when they were studying the effects of faults in the breast cancer gene, BRCA2, on mitochondria. People who inherit a faulty copy of BRCA2 have a high risk of developing cancers of the breast, ovary, pancreas, prostate and other organs. The researchers found that cells with faulty BRCA2 have high levels of oxidative stress, and display several signs that the replication of their mitochondrial DNA is blocked. The team found that similar problems also occur in cells carrying faulty copies of genes implicated in human neurodegenerative disorders. So, their research highlights how oxidative stress could accelerate ageing-related human diseases like cancer or neurodegeneration by damaging mitochondria.

Prof. Venkitaraman, lead author of this study said,

“When studying the breast cancer gene BRCA2, we serendiptiously discovered a specific molecular mechanism through which oxidative stress damages mitochondria, the ‘power stations’ which supply energy to human cells. We think this discovery could yield further clues as to how oxidative stress may increase the risk of ageing-related diseases, and open future opportunities for treatment.”

The team’s findings were published in the journal Cell Reports on 3 August 2021. Read the full paper here.