Mitofusin

A family of outer-mitochondrial-membrane proteins supporting GTP-dependent membrane fusion. Loss-and-rescue experiments establish a role beyond merely correlating protein abundance with network shape.^[ref]

Mfn2 is an outer-mitochondrial-membrane mitofusin involved in GTP-dependent mitochondrial fusion. Its activity helps join the outer boundaries of neighbouring mitochondria, enabling later mixing of their contents through the coordinated fusion machinery. Mfn2 can associate with itself or with Mfn1. ^[ref]

In the mouse study, loss of Mfn2 produced fragmented mitochondria in embryonic fibroblasts and a placental defect distinct from the phenotype of Mfn1 deficiency. These comparisons show why two related proteins need not be interchangeable in every cell type. Network fragmentation alone does not identify whether reduced fusion or increased fission caused the change.

Mfn1 is an outer-mitochondrial-membrane mitofusin that promotes mitochondrial fusion through a GTP-dependent mechanism. It forms complexes with itself and with Mfn2. Fusion lets separate mitochondria exchange components, contributing to maintenance of a functional mitochondrial network. ^[ref]

Mouse fibroblasts deficient in Mfn1 showed a severe reduction in fusion and fragmented organelles. Rescue experiments supported a causal role for Mfn1, while comparison with Mfn2-deficient cells revealed overlapping and distinct functions. The combination of genetic loss, direct fusion assessment and rescue is more informative than inferring a fusion mechanism from a still image of mitochondrial shape.