Taz1p localizes to both inner and outer mitochondrial membranes.
Barth syndrome is a human disorder in which mitochondrial dysfunction, including disturbed lipid composition, leads to cardiac myopathy and other problems. Previous work showed that the yeast tafazzin protein (Taz1p) is a suitable model for the syndrome and that Taz1p localizes to mitochondria.
In the current work, the authors found that Taz1p localized to the inner and outer membranes of the mitochondria, but only to the leaflets that face the intermembrane space. A central loop in the Taz1p protein inserted into the membranes and hung onto them as tenaciously as do transmembrane proteins. But the loop did not extend all of the way through the membrane as is typical for transmembrane proteins. The bulk of Taz1p protruded into the intermembrane space.
Four of the disease-causing point mutations in tafazzin lay in the putative membrane anchor loop. Introduction of each of these mutations into Taz1p altered its association with the membrane. Three of the changes caused Taz1p to localize to the mitochondrial matrix. In the fourth case, the protein remained in the intermembrane space but formed different macromolecular complexes relative to the wild-type protein.
Claypool et al. conclude that tafazzin function is sensitive to both mislocalization and disruption of molecular interactions. The question now is just what that function is. The unusual localization of the protein is consistent with it being an acyltransferase for the mitochondria-specific phospholipid cardiolipin (and perhaps for lyso-phosphatidylcholine), but enzyme assays will be needed to answer the question for sure. 
