Just as your skeleton helps your body move, fine skeleton-like filaments within your cells help cellular structures move. Researchers have developed an imaging method that lets them monitor a small subset of these filaments called actin.
With the new imaging technique, the Salk team has been able to home in on how actin mediates an important function: helping the cellular “power stations” (known as mitochondria) divide in two. The work could provide a better understanding of mitochondrial dysfunction, which has been linked to cancer, aging, and neurodegenerative diseases.
Mitochondrial fission is the process by which these energy-generating structures, or organelles, divide and multiply as part of normal cellular maintenance; the organelles divide not only when a cell itself is dividing but also when cells are under high amounts of stress or mitochondria are damaged. However, the exact way in which one mitochondrion pinches off into two mitochondria has been poorly understood, particularly how the initial constriction happens. Studies have found that removing actin from a cell entirely, among many other effects, leads to less mitochondrial fission, suggesting a role for actin in the process. But destroying all the actin causes so many cellular defects that it’s hard to study the protein’s exact role in any one process, the researchers say.
Manor and his colleagues developed a new way to image actin. Rather than tag all the actin in the cell with fluorescence, they created an actin probe targeted to the outer membrane of mitochondria. Only when actin is within 10 nanometers of the mitochondria does it attach to the sensor, causing the fluorescence signal to increase.
Rather than see actin scattered haphazardly around all mitochondrial membranes, as they might if there were no discrete interactions between actin and the organelles, Manor’s team saw bright hotspots of actin. And when they looked closely, the hotspots were located at the same locations where another organelle called the endoplasmic reticulum crosses the mitochondria, previously found to be fission sites. Indeed, as the team watched actin hotspots light up and disappear over time, they discovered that 97 percent of mitochondrial fission sites had actin fluorescing around them. (They speculate that there was also actin at the other 3 percent of fission sites, but that it wasn’t visible).
By altering the actin probe so it attached to the endoplasmic reticulum membrane rather than the mitochondria, the researchers were able to piece together the order in which different components join the mitochondrial fission process. The team’s results suggest that the actin attaches to the mitochondria before it reaches the endoplasmic reticulum. This lends important insight toward how the endoplasmic reticulum and mitochondria work together to coordinate mitochondrial fission.