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A METEORic role

Researchers find a surprising new function of some mitochondria involving cellular migration

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The thesis project research of Madeleine Marlar-Pavey, an M.D./Ph.D. student at UT Southwestern, revealed a surprising new role for a certain types of mitochondria beyond generating energy for cells.

UT Southwestern researchers have discovered a specialized type of mitochondria that help cells migrate.

The mitochondria, which the researchers have named METEORs for their shape, live in the tips of filopodia – finger-like projections at the leading edge of migrating cells. METEORs have a different biochemical makeup than typical mitochondria, a finding that supports the idea that these mitochondria are specialized for a different task than the usual one of generating energy for cells.

The study, published recently in Current Biology, is an interesting beginning to learning more about various roles mitochondria play, the researchers said.

“This work may have important implications in disease,” said study senior author Jonathan Friedman, Ph.D., Assistant Professor of Cell Biology. “For example, cell migration is often altered and utilized by cancer cells as they become metastatic. Thus, preventing these mitochondria from targeting filopodia could exploit a vulnerability of cancer cells.”

Dr. Friedman in white coat in lab
Jonathan Friedman, Ph.D., Assistant Professor of Cell Biology, was the senior author on the METEORs mitochondria study.

Mitochondria are best known as the “powerhouses of the cell” because they generate the molecule ATP, which stores the chemical energy driving many cellular processes. However, mitochondria also play roles in calcium storage, immune response, and other functions.

“It’s very exciting,” said Madeleine Marlar-Pavey, an M.D./Ph.D. student who led the work as her thesis project. “We’ve joined a group of people who are finding surprising new behaviors of mitochondria.”

The unexpected finding came when the researchers were studying MICOS, a protein complex that helps shape the inner structure of mitochondria. They noticed one of the proteins in MICOS was concentrated at the edges of mitochondria in cultured osteosarcoma cells.

“We just happened to notice something interesting and cool and decided to follow it,” Dr. Friedman said. “We are learning new ways in which mitochondria can perform a division of labor within cells, and this finding adds to a growing list of new types of mitochondria.”

Using immunolabeling, genetic knockdowns, and other techniques, they found about 40% of cells contained METEORs in very small numbers – usually three or fewer per cell.

microscopic image of mitochondria cells
METEOR mitochondria (labeled in green and magenta) localize in the cell periphery within filopodia. The gray labeling marks the boundary of the cell.

The researchers confirmed the filopodia that contained METEORs were about twice as long as the filopodia without METEORs. They also found that when cells were cultured on collagen, which increases cell migration, the number of METEORs in filopodia went up.

The exact function of these mitochondria in cell migration remains under study, because they’re low in the proteins that drive energy production – the most widely recognized function of mitochondria.

However, the METEORs were enriched in a protein called MCU, which transports calcium from the cell’s cytoplasm – the fluid surrounding its internal structures – into the mitochondria, where it can be used for energy production or temporarily stored before being released back into the cell. How this function of MCU might support cell growth or migration remains to be explored.

In addition, the work was done on one cell type, and it remains open whether METEORs form in other cells; for instance, neurons rely on filopodia for the formation of axons and dendrites during development, Dr. Marlar-Pavey said.

Dr. Friedman is a Southwestern Medical Foundation Scholar in Biomedical Research.

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