Harvard Medicine

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The Insults of Injury

Trauma-related mitochondrial damage may trigger inflammation.

Mitochondria are minute organelles that float, sometimes by the thousands, within the cytoplasm of our cells. Distant relatives of bacteria, these tiny powerhouses produce the energy-rich molecules that our cells consume for such demanding activities as replication, movement, and repair. But despite their intracellular residency, mitochondria remain genetically discrete, housing DNA that is molecularly unrelated to that within the cell’s own nucleus. Research at Beth Israel Deaconess Medical Center now indicates that it may be precisely this part-and-apart nature of mitochondria that makes them culpable in a form of inflammation that arises from cellular injury and unregulated cell death rather than from infection.

“Blunt-force trauma,” says team member Carl Hauser, an HMS visiting professor of surgery and a trauma and critical-care specialist at the medical center, “can kill significant amounts of tissue, as can burns, chemotherapy, and many diseases. We wondered whether tissues that die from trauma release a sort of molecular debris not usually encountered by the body’s immune system.”

In research published in the March 4, 2010, issue of Nature, Hauser and colleagues report that detritus, particularly mitochondria, from traumatized cells triggered a systemic inflammatory response that—when tested in human white blood cells, rats, and mice—was akin to infection-related sepsis in humans. Clinically, traumatic injury to tissue initiates an immune response much like that waged against foreign invaders such as viruses or bacteria. Unlike immune responses acquired through vaccinations and other preventive measures, the body’s response to foreign material is innate, cued from birth to respond immediately to the molecular patterns of external pathogens—like the patterns carried by that bacterial relative, the mitochondrion. In trauma-induced immune responses, however, the body’s fight focuses on itself. Thus, when freed from their cellular confines, the mitochondrial residents that power a cell’s health and functioning become tools to its destruction.

The findings could spur the development of new tests to discriminate infective from non-infective inflammation as well as new strategies for trauma management.

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