Mitochondrial homeostasis requires the coordination of fusion and fission events. The mammalian dynamin-related protein Drp1 (called Dnm1 in yeast) forms coils around mitochondria and mediates fission, but how fission sites are selected was unclear. Voeltz and colleagues now show that fission preferentially occurs at sites of endoplasmic reticulum (ER)–mitochondria contact (Science http://dx.doi.org/10.1126/science.1207385).

High-resolution microscopy of ER–mitochondria contact sites revealed that the ER wraps tightly around the mitochondria to form constrictions in the mitochondrial network. Intriguingly, Drp1/Dnm1 accumulation, and mitochondrial fission, occurred preferentially at these contact sites in both mammalian and yeast cells. The outer mitochondrial protein Mff is essential for Drp1 localization and mitochondrial fission, and ER–mitochondria contact and mitochondrial constriction occurs even when Mff or Drp1 are depleted.

The authors propose that ER-mediated constriction of mitochondria might facilitate the formation of Drp1/Dnm1 coils and subsequent fission, but also acknowledge that the ER might participate in mitochondrial fission directly — possibilities that will be important and interesting to address.