Specialized high-capacity mitochondria fuel cell invasion.

Cell invasion through basement membrane (BM) is energetically intensive. How cells produce high ATP levels to power invasion is understudied. By endogenously tagging 20 mitochondrial proteins, we identified a specialized mitochondrial subpopulation within the C. elegans anchor cell (AC) that localizes to the BM breaching site and generates elevated ATP levels to fuel invasion. These electron transport chain (ETC)-enriched high-capacity mitochondria are compositionally unique, harboring increased protein import machinery and dense cristae enriched with ETC components. High-capacity mitochondria emerge at the time of AC specification and depend on the AC pro-invasive transcriptional program. Finally, we show that netrin signaling through an Src kinase directs microtubule polarization, facilitating metaxin adaptor complex-dependent ETC-enriched mitochondrial trafficking to the AC invasive front. Our studies reveal that an invasive cell produces high ATP levels by generating and localizing high-capacity mitochondria. This might be a common strategy used by other cells to meet the energetically demanding processes.