Mitochondria are remarkable shape-shifting organelles that have long been understood as the powerhouses inside our cells. But relatively little is known about how the constant fission and fusion of these tiny energy generators impacts stem cell function and tissue regeneration.
Now, compelling new research from Dr. Mireille Khacho’s lab at the University of Ottawa Faculty of Medicine reveals a starring role for mitochondrial dynamics within adult muscle stem cells—those unique and primitive cells that serve as the body’s raw material for muscle renewal and repair.
Published today in the print edition of the peer-reviewed journal Cell Stem Cell, the study found that mitochondria’s shape transitions as they elongate and divide are in fact regulating the dormant state of adult muscle stem cells.
The new findings could be an important revelation because adult muscle stem cells –—which typically exist in a dormant state known as quiescence— are essential for tissue stability. Dormancy is crucial to these cells’ longevity and they require a delicate balance. They get roused from their protective state when activated for renewal and when repairing tissue that suffers an injury or has been corroded by disease.
In essence, her lab suggests a wide-ranging repertoire for mitochondria. Not only do they act as internal sensors and communicators, but their fragmentation plays a big part in overall stem cell maintenance and functioning. Through a series of manipulations with a unique mouse model, the researchers showed that the essential mitochondrial shaping protein OPA1 regulates the dormant state of adult muscle stem cells. And the chronic loss of this protein and persistent fragmentation leads to severe muscle stem cell defects.
Dr. Khacho’s team says the findings show for the first time that the protein OPA1—one of the main regulators of mitochondrial fusion—is essential for muscle stem cell maintenance and function. They pieced together a connection between the depletion of stem cells and mitochondria becoming imbalanced and dysfunctional.
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