A role for actin in mitochondrial division: effects across two membranes
We have elucidated a pathway by which mitochondrially-associated actin filaments participate in mitochondrial dynamics. An increase in cytoplasmic calcium activates actin polymerization through the ER-bound formin INF2, which in turn stimulates the dynamics of both the inner and outer mitochondrial membranes. INF2-mediated actin filaments induce an increase in ER-mitochondrial contact, which facilitates a transient increase in mitochondrial matrix calcium, leading to constriction of the IMM in a Drp1-independent manner. In addition, INF2-mediated actin polymerization stimulates Drp1 oligomerization, leading to constriction of the OMM. A portion of Drp1 oligomerization initiates on ER, through an ER-bound population of the Drp1 receptor Mff. I will also discuss other mechanisms for mitochondrially-associated actin polymerization, and how they differ from the INF2-mediated pathway.