Locating a mitochondrial scaffold on the map

T he ability of mitochondria to perform numerous different functions is refl ected in the organelle's complex architecture. The mitochondrial inner membrane, in particular, is organized into distinct regions that carry out specialized functions (1). Boundary regions are where the inner membrane contacts the outer membrane to facilitate protein import and respiratory complex assembly. Once assembled , respiratory complexes concentrate in cristae, inner membrane folds that project into the mitochondrial matrix. Connecting these two inner membrane regions are tubular structures called cristae junctions. Hoppins et al. uncover a protein complex that organizes the mitochondrial inner membrane into these distinct domains (2). Jodi Nunnari, who works at the University of California, Davis, is interested in the various functions of mitochondria. " We're really interested in fi guring out how they're all integrated with each other, " she says, " but that system-wide view is hard to get at using classical cell biological approaches. " Nunnari therefore teamed up with several researchers, including Jonathan Weiss-man from the University of California, San Francisco, whose lab has helped develop methods to comprehensively map the interactions between large sets of yeast genes (3). " These approaches allow you to explore functions without envisioning, a priori, all the important processes of the cell, " Weissman explains. " It removes personal bias from your analysis. " Weissman is also interested in the physical and functional links between mito-chondria and the endoplasmic reticulum. The researchers therefore quantifi ed the interactions between 1,482 yeast genes encoding ER and mitochondrial proteins by mating single mutant strains to each other and measuring the growth of the resulting double mutants. Strong changes in growth indicate a signifi cant interaction between the two alleles, and genes with similar interaction patterns—what Weissman describes as a " high-resolution phenotype " —are likely to share a common function. The resulting interaction network, which the researchers named " MITO-MAP, " showed that mitochondria and the ER generally have separate functions, though a protein complex called ERMES, which physically links the two organelles (4), helps them cooperate in phospholipid synthesis and mitochondrial DNA inheritance. MITO-MAP also revealed the existence of a new protein complex within mitochon-dria themselves. A cluster of four genes— FCJ1, AIM5, AIM13, and AIM37—had similar interaction profi les with a variety of inner and outer membrane proteins. " We never would have seen this complex without taking this systems-wide view, " Nunnari says. Im-munoprecipitation experiments …