Position of power

Abstract

Migrating leukocytes are “rear-wheel drive cells,” says Antonella Viola. Her group finds that mitochondria, the cell's engines, shift to the back of neutrophils to power cell movement, as revealed in Campello et al. (page 2879). Figure 1 A migrating leukocyte gets its rear in gear by shifting mitochondia (red) to its back end. Mitochondria can accumulate in regions of the cell with high energy demands, such as at the active growth cones of developing neurons and at the neuromuscular synapse. Viola and her team wondered whether mitochondria might also adopt a specific intracellular location in migrating cells. Leukocytes migrate to immunological battlegrounds in response to chemokines, and the team now shows that, in vitro, this chemotaxis is coupled with movement of mitochondria to the rear of the cell, known as the uropod. Although the leading edge of the leukocyte sends out exploratory protrusions as these cells migrate, the uropod contains both the adhesion machinery and the myosin motors essential for cell movement, explains Viola. The discovery that mitochondria also relocate to the uropod leads Viola to suggest that, in the mechanics of cell migration, the power comes from the push. Mitochondrial movement along microtubules requires the mitochondria to first divide into smaller, mobile units. By preventing this division, the team revealed that mitochondrial relocation to the uropod was not just coupled with, but necessary for, leukocyte migration. Boosting the mitochondrial energy production in these cells compensated for a lack of relocation, suggesting that mitochondrial movement was required for localizing ATP production at the uropod. Indeed, the team showed that inhibiting mitochondrial, but not cytoplasmic ATP production, reduced activation of myosin motors in the uropod but not elsewhere in the cell. In addition to various leukocytic cell types, migrating human breast cancer cells also relocate their mitochondria to the rear, the team found. This suggests that inhibiting the division of mitochondria, and thus their movement, might be a potential intervention strategy for preventing tumor metastasis.