Silencing MiD49 or MiD51 or augmenting an miR-107 mimic reversed established atherosclerosis in vivo, highlighting the contribution of the miR-107–HIF-1α–MiD51–Drp1 axis to the pathophysiology of atherosclerosis and the viability of this pathway as a target for new therapeutic strategies. Here, MIEF2 is linked to atherosclerosis.