To produce energy, mitochondria need molecular oxygen. As a side product of this cellular respiration, mitochondria also produce highly reactive oxygen radicals which damage and degrade many cellular components, including DNA. Cellular senescence, as well as other aging processes, has been thought to be linked with chronic, long-term exposure to free radicals.
Cells defend themselves from the free radicals in various ways, including antioxidant enzymes such as superoxide dismutases (SOD). For example, mice lacking the mitochondrial SOD2 enzyme die soon after birth. However, reduced SOD2 activity results in very specific type of heart disease, cardiomyopathy, which is caused by the loss of heart muscle cells and successive replacement with connective tissue. This replacement fibrosis is similar to the aging related cardiomyopathy in humans. Mice with reduced SOD2 also have high levels of mtDNA mutations and difficulties in its replication. When these problems were overcome by transgenic expression of mitochondrial Twinkle-helicase also the heart cells survived and the cardiomyopathy was prevented despite the ongoing free radical exposure.
Further investigation revealed that the improved mtDNA integrity resulted in specific type of cell signaling, which inhibited programmed cell death and directed the heart cells towards damage-tolerance mode.
Because free radicals are an important source of damage after a heart stroke as well as in normal heart aging processes, the published study will help to open new opportunities in therapy as well as promoting healthy aging.
For more information contact:
Dr. Jaakko Pohjoismäki, Department of Biology, University of Eastern Finland
e-mail: Jaakko.Pohjoismaki@uef.fi, tel. +358-50-5744745.
(1) Pohjoismäki JL, Williams SL, Boettger T, Goffart S, Kim J, Suomalainen A, Moraes CT, Braun T. (2013). Overexpression of Twinkle-helicase protects cardiomyocytes from genotoxic stress caused by reactive oxygen species. Proc Natl Acad Sci U S A. doi: 10.1073/pnas.1303046110 http://www.pnas.org/content/early/2013/11/06/1303046110.abstract