The last wall of defense to prevent extreme and deleterious mitochondrial fusion.

Mitochondria are dynamic organelles adapting their morphology by cycles of fission and fusion events to control cellular homeostasis. In this issue of The EMBO Journal, Murata and colleagues (2020) show that lack of mitochondrial division leads to safeguard mechanisms, induced by transient mitochondrial membrane depolarization and activation of the metalloprotease OMA1, to prevent extreme mitochondrial fusion and to maintain optimal mitochondrial bioenergetics.