This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: If your car's engine develops a stutter, that's generally a sign that you should go to a mechanic before it stops running. We tend to think the same way about our bodies: When something's broken, something bad usually follows.
There might, however, be at least one exception to this rule. Mutations in the energy-production pathways of mitochondria, the organelles responsible for making the energy cells need to function and survive, are normally associated with aging and several disease states. However, there's a decades-old paradox in aging biology in which certain disturbances in mitochondrial function can counterintuitively help extend an organism's life span.
This effect has not just been observed in Caenorhabditis elegans, the transparent worm in which this phenomenon was discovered; it's also been observed across evolution and even in humans. In fact, metformin, a drug approved for the treatment of type 2 diabetes, is a mild mitochondrial inhibitor that is currently being developed as a potential anti-aging drug. And yet—scientists have not yet been able to parse what makes mitochondrial inhibition beneficial in some contexts but pathological in others.
Kris Burkewitz, an assistant professor of cell and developmental biology, has been working to understand how cells respond and adapt to mitochondrial impairment. In a recent paper in Nature Communications, the Burkewitz lab explored how communication between the mitochondria and other organelles might be helping cells adapt to mitochondrial dysfunction. "Much of the past research has focused on understanding how mitochondria themselves adapt to stress, but really the cell operates as a community of many different organelles," Burkewitz said.
"One of our goals was to take a more holistic approach and ask how other parts of the cell might be involved in adapting to mitochondrial dysfunction." Emerging research has shown that the endoplasmic reticulum, a second essential metabolic hub of the cell, interacts closely with mitochondria and regulates their functions through calcium signals, among other pathways. True to the research team's goal of understanding connections between different parts of the cell, they found that the major player in ER calcium signaling, a conserved ion channel called the IP3 receptor, is essential for the ability of a specific mitochondrial mutation to extend life span. Mutations in energy-production pathways trigger mitochondria to grow and expand as a way to overcome their reduced function.
The study showed that an essential aspect of successful adaptation to mitochondrial stress in the long-lived worms is the ability to keep these dysfunctional mitochondrial networks from growing excessively large and interconnected. The team demonstrated that, to prevent the uncontrolled expansion of mitochondria, calcium released by the ER activates the remodeling of the actin cytoskeleton, which earlier research had shown can act as restrictive mitochondrial "cages." "We've identified new genetic links between ER calcium signaling, actin remodeling and the turnover dynamics of mitochondrial networks in these aging contexts, but there are many molecular details to fill in before we fully understand how these pathways are connected," Burkewitz said. Discover the latest in science, tech, and space with over 100,000 subscribers who rely on Phys.org for daily insights. d research that matter—daily or weekly.
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