The cells energy production organelle is often taken for granted on a daily basis, supplying the cell with a pool of chemical energy molecules critical for normal metabolic function. However, this unique organelle plays major roles in signaling, differentiation, and cell death. Moreover, since it contains its own DNA, it has been frequently linked to an individuals inherited risk for diabetes, heart disease, and even cancer.

Now, scientists at the Icahn School of Medicine at Mount Sinai have developed a powerful new tool they believe may assist researchers in explaining the disparity between individuals with bad health habits, some of whom get sick and those that do not. The findings from this study were published online recently in Nucleic Acids Research through an article entitled “Stable heteroplasmy at the single-cell level is facilitated by intracellular exchange of mtDNA”

Over the past several years, scientists have uncovered evidence that discrepancies in mitochondrial energy production are an underlying cause of several diseases. Unfortunately, scientists trying to determine the contribution of mitochondrial DNA (mtDNA) to an individual’s risk for a disease have been stymied by the organelle’s inherent heteroplasmy, which is the presence of more than one type of DNA in different sets of mitochondria.      

“Researchers have struggled to sequence mtDNA accurately and in a cost effective manner,” explained Ravi Sachidanandam, Ph.D., assistant professor of oncological sciences at the Icahn School of Medicine at Mount Sinai and senior author on the current study. “The technique we have developed will allow us to identify dysfunction within mitochondria and makes mtDNA a useful biomarker as well as a potential therapeutic target in cancer and many inherited diseases.”

Dr. Sachidanandam and his team developed a new mitochondrial purification and sequencing technique, called Mseek, which they used to accurately identify heteroplasmy within an individual’s mtDNA, with greater sensitivity and specificity than previous mtDNA sequencing techniques.

Specifically, Mseek uses a set of enzymes to delete nuclear DNA, followed by purification and separation of mtDNA, which yields a very pure sample for sequencing applications. Additionally, the researchers were able to apply the Mseek technique across several cell lines, establishing mtDNA “fingerprints” for each sample. From these studies the Mt. Sinai team was able to conclude that heteroplasmy is stably maintained at the single-cell level over multiple cell and organellar divisions.     

“We hypothesized that heteroplasmy could be stabilized by intercellular exchange of mtDNA,” stated Dr. Sachidanandam. “Our results demonstrated the exchange of mtDNA is possible and heteroplasmy can be maintained stably through this mechanism. This technique could provide a novel platform to investigate features of heteroplasmy in normal and diseased state and in the future, the exchange mechanism could be used as a treatment that targets bad mtDNA and exchanges it with good mtDNA.”

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