Membrane Bending Energy and Tension Govern Mitochondrial Division

Abstract

Many molecular factors required for mitochondrial division have been identified; however, how they combine to physically trigger division remains unknown. Here, we report that constriction by the division machinery does not ensure mitochondria will divide. Instead, potential division sites accumulate molecular components and can constrict before either dividing, or relaxing back to an unconstricted state. Using time-lapse structured illumination microscopy (SIM), we find that constriction sites with higher local curvatures – reflecting an increased membrane bending energy – are more likely to divide. Furthermore, analyses of mitochondrial motion and shape changes demonstrate that dividing mitochondria are typically under an externally induced membrane tension. This is corroborated by measurements using a newly synthesized fluorescent mitochondrial membrane tension sensor, which reveal that depolymerizing the microtubule network diminishes mitochondrial membrane tension. We find that under reduced tension, the number of constrictions is maintained, but the probability that constrictions will divide is concomitantly reduced. These measurements allow us to establish a physical model, based on in situ estimates of membrane bending energy and tension, which accounts for the observed fates of mitochondrial constriction events.