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An Unexpected Discovery in Brain Cells
Recent research has uncovered an intriguing phenomenon involving DNA found in the nuclei of brain cells, where it has not typically been observed. This study reveals that fragments of mitochondrial DNA, normally confined to mitochondria—the powerhouses of cells—are frequently integrating into the nuclear genome of brain cells.
Furthermore, these mitochondrial insertions appear to correlate with longevity. In a study involving nearly 1,200 older individuals, findings suggest that those possessing higher quantities of these insertions tended to have shorter lifespans. Martin Picard from Columbia University and his colleagues presented these findings in the journal PLOS Biology on August 22. Their research indicates that understanding or even manipulating these insertions may eventually offer insights into age-related diseases or disorders linked to mitochondrial dysfunction.
Insights into Mitochondria’s Role
Mitochondria are widely recognized for their primary function as cellular energy producers, but their roles extend far beyond energy metabolism. According to Picard, these organelles can influence various cellular behaviors through multiple mechanisms. One of these is the transport of their own DNA into the cell nucleus, a process known as numtogenesis. While this has been observed previously in specific cell types such as cancer and reproductive cells, it had yet to be documented in human brain tissue.
To investigate this, Picard’s team analyzed stored postmortem brain and blood samples from 1,187 older adults. They meticulously measured the frequency of mitochondrial DNA insertions across various brain regions, including the dorsolateral prefrontal cortex (DLPFC) and the cerebellum. The DLPFC plays a crucial role in cognitive functions, such as decision-making, while the cerebellum is vital for coordination and balance.
The results were surprising: brain tissues exhibited a remarkable abundance of mitochondrial insertions, with DLPFC cells possessing, on average, 15 times more insertions than those in blood cells, and five times more than cerebellar cells. This disparity may hold significance given that the DLPFC is often implicated in numerous age-related and neurodegenerative conditions, whereas the cerebellum usually remains unaffected, according to Picard. Notably, the research team found a correlation between increased mitochondrial insertions in the DLPFC and decreased lifespan, suggesting that numtogenesis might be a factor linked to longevity.
The Health Implications of Mitochondrial Insertions
The research team also examined living skin cells to further understand how aging affects mitochondrial insertion rates. Their experiments indicated that these cells acquired an insertion approximately every 13 days under laboratory conditions. Interestingly, stressors, including certain genetic mutations or drug treatments, heightened the frequency of insertions. Specifically, drugs such as dexamethasone and oligomycin were found to elevate the rates of numtogenesis, while skin cells from individuals lacking the gene SURF1—linked to a severe mitochondrial disorder known as Leigh syndrome—displayed an almost fivefold increase in insertion rates compared to control cells.
Picard posits that numtogenesis could be a mechanism by which mitochondrial dysfunction contributes to disease processes and premature mortality, particularly in conditions like Leigh syndrome.
This study marks a significant advancement in understanding the role of numtogenesis in human health, indicating that it occurs in brain tissue and varies across different body areas. However, the specific health implications of these mitochondrial insertions remain uncertain. According to Anabelle Decottignies, a molecular biologist at the University of Louvain, we have yet to establish whether these insertions have detrimental effects on tissue function.
Miria Ricchetti from the Pasteur Institute highlights the need for further research to identify the locations in the nuclear genome where mitochondrial DNA is inserted. Such knowledge would be crucial for elucidating the impact of these insertions on cellular function.
Looking ahead, Picard emphasizes the necessity of exploring the relationship between mitochondrial insertions and disease development. He suggests that if a connection is confirmed, these insertions might serve as valuable indicators of health, theorizing that healthier individuals may accumulate fewer insertions over time.
Source
www.sciencenews.org