Dysfunctional Mitochondria Can Influence Nuclear Gene Expression

Credit: D. Burnette, J. Lippincott-Schwartz/NICHD

New research is confirming that mitochondrial DNA can exit mitochondria and interact with DNA in the nucleus – influencing and controlling cellular behaviour  

Mutations in mitochondrial DNA are closely linked to a number of conditions including heart disease, but exactly how these mutations contribute to disease risk isn’t fully known. During aging certain cells also appear to accumulate faulty mitochondria, which then impacts on a range of cellular functions. A new research study has now indicated that mitochondria DNA can in fact leave its host and travel to the cell nucleus; regulating gene expression. 

An intimate relationship

The new study is testament to how complex and intertwined our cells and mitochondria have become in their symbiotic relationship. Researchers discovered there is a kind of feedback system between the cell and its mitochondria, and that both effectively talk to one another directly through DNA interaction, in addition to other known mechanisms. 

“We found evidence that mitochondria DNA and nuclear DNA ‘talk to each other’, and these interactions aren’t random. We think the connections we detected are part of a feedback system between mitochondria and the cell nucleus that may influence how humans grow and develop throughout life”

When feedback goes wrong

Human mitochondria DNA encodes for only 37 genes, the rest have been slowly moved during evolution into the nucleus 

This feedback system is normally extremely valuable, but the researchers suggest that harmful mutations in mitochondrial DNA could lead to detrimental feedback, in which the nucleus is unable to pick up on faulty mitochondria or is somehow influenced by the altered DNA. During these conditions or even perhaps the aging process itself, specific mitochondrial DNA alterations could prevent correct nuclear communication; leading to a cascade of failures that impair energy metabolism for example. Dysfunctional mitochondria understandably cause metabolic deficits or perhaps even oxidative damage in some cases, but this research affirms that dysfunction in our cellular batteries can work through another mechanism too – nuclear DNA interaction and feedback. When this communication fails or is twisted somehow, it may contribute to disease risk. 

“This study adds to our understanding of the way in which changes to mitochondria manifest as disease. Further research could yield new treatment avenues. Next, we need to figure out exactly how the two sets of DNA talk to each other, and the effects of that talking”

The SENS Foundation is attempting an innovative project attempting to bring mitochondria genes into the nucleus to shield them from harm, but it may be that finding a way to restore correct communication in another manner could also resolve some of these dysfunctional mitochondria somehow. 

Read more at MedicalXpress