page 167). Mgm1's energy dependence may ensure that tired mitochondria get left behind.
Mgm1 can be found in the mitochondrial intermembrane space in two forms, the shorter of which (s-Mgm1) is generated by protease cleavage of the long form (l-Mgm1). The authors find that a balance between the two forms maintains mitochondrial morphology—deviation from a 1:1 ratio in either direction causes fragmentation. Although little is known about Mgm1 function, this need for balance might be explained if s- and l-Mgm1 work as heterodimers.
Balanced production of the two forms depends on a hydrophobic stretch in l-Mgm1 following the targeting sequence. Mutations that further increased its hydrophobicity favored production of the long form, whereas a decrease in hydrophobicity favored the short form. This suggests that hydrophobic-dependent lateral movement of l-Mgm1 out of the import channel into the inner membrane prevents its cleavage.
But if the protein instead translocates further into the mitochondrial import channel, s-Mgm1 is formed. This translocation depends on the protein import motor (including the ATP-dependent chaperone Ssc1), which drives the NH2 terminus of Mgm1 into the matrix until a second hydrophobic domain reaches the inner membrane. There, the second domain is cleaved by the Pcp1 protease to produce s-Mgm1.
Cells impaired in ATP synthesis made mostly l-Mgm1 and had a fragmented mitochondrial network. The need for energy during Mgm1 import might ensure that mitochondria that are inept in ATP production, perhaps due to oxidative damage, are excluded from the network and are thus not inherited by daughter cells. ▪