To Fis or not to Fuse? This is the question!

Mitochondrial shaping proteins are categorized as fusion and fission factors based on their opposing actions on the architecture of mitochondria. Mammalian Fis1 fragments mitochondria into small units and was initially considered a major mitochondrial fission factor, with this major role being challenged. Yu et al () define that Fis1 induces mitochondrial fragmentation by blocking mitochondrial fusion. This study highlights the limitation of categorizing mitochondrial dynamics proteins based on architecture measurements, given the general tendency to associate fragmentation with activation of fission.