Fig 12. Working model illustrating the role of Yta4 in inhibiting mitochondrial fission.

Mitochondrial fission is mediated by Dnm1, which is recruited to the mitochondrial outer membrane by Fis1 via Mdv1. Note that Fis1, Mdv1, and Dnm1 are the 3 components of the mitochondrial divisome [25]. Yta4 interacts with Fis1, Mdv1, and Dnm1 to inhibit mitochondrial fission by different mechanisms (top diagram). (1) Yta4 likely functions as a canonical dislocase to maintain the homeostasis of the TA protein Fis1 on the mitochondrial outer membrane, and the delocalization of Fis1 from mitochondria is significant when Yta4 is overexpressed, (2) Yta4 and Dnm1 interact with Mdv1 in a competitive manner to inhibit the recruitment of Dnm1, and (3) Yta4 inhibits the GTPase activity of Dnm1 likely through a dynamic interaction. Thus, the absence of Yta4 promotes efficient mitochondrial fission (bottom diagram). TA, tail-anchored; WT, wild-type.