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Tanneti, N.S., Landy, K., Joyce, E.F., and Dawson, D.S. (2009). The synaptonemal McKim, K.S. (2011). A pathway for synapsis complex protein Zip1 promotes bi-orientation Department of Biology, New York University, initiation during zygotene in Drosophila of centromeres at meiosis I. PLoS Genet. 5, New York, NY 10003, USA. oocytes. Curr. Biol. 21, 1852–1857. e1000771. E-mail: [email protected] 7. Liebe, B., Alsheimer, M., Hoog, C., 11. Newnham, L., Jordan, P., Rockmill, B., Benavente, R., and Scherthan, H. (2004). Roeder, G.S., and Hoffmann, E. (2010). The Telomere attachment, meiotic chromosome synaptonemal complex protein, Zip1, promotes condensation, pairing, and bouquet stage the segregation of nonexchange chromosomes DOI: 10.1016/j.cub.2011.10.023 Organelle Dynamics: ER Embraces yeast or Drp1 in mammals. Members of the dynamin family are large GTPases Mitochondria for Fission that self-assemble into large helical oligomers that wrap around cellular membranes. Membrane tubulation The endoplasmic reticulum and mitochondria are engaged in an intimate and/or fission is then achieved by relationship: they establish extensive contacts, exchange lipids and calcium, mechanochemical forces released and coordinate their activities in cell life and death. Recent research has upon GTP hydrolysis [3]. The molecular revealed a new role for the endoplasmic reticulum in promoting mitochondrial machinery of mitochondrial fission has division. been studied in great detail, both in yeast and in mammals. In yeast, Benedikt Westermann potential to dissipate metabolic a mitochondrial outer membrane energy. It also allows intermixing and protein, Fis1, and a soluble adaptor Cellular organelles were long regarded exchange of mitochondrial content and protein, Mdv1, promote the assembly as separate entities that provide complementation of mitochondrial of cytosolic Dnm1 on the mitochondrial secluded compartments tailored for gene products, a process thought to surface, driving membrane scission specific cellular or metabolic reactions. counteract the decline of mitochondrial [4–6]. Similarly, mammalian Drp1 can This view has changed as it has been functions during aging. Mitochondrial be recruited to the mitochondrial recognized that organelles are highly fission, on the other hand, is required to surface by Fis1, albeit without the dynamic and interdependent. It is now generate organelles that are small participation of an Mdv1 homologue becoming clear that the intricate enough to be transported by molecular [7]. In addition, the outer membrane of architecture of a eukaryotic cell can be motors along the cytoskeleton. This is mammalian mitochondria contains established and maintained only particularly important in large, a Fis1-independent division protein, through coordinated and cooperative differentiated cells, such as neurons, Mff, which recruits Drp1 and is activity of its constituents. Now, in and during cell division. Moreover, essential for mitochondrial fission [8,9]. a recent article published in Science, mitochondrial fission is important for Although these and many other studies Friedman et al. [1] report that the the release of cytochrome c from the provided a wealth of data allowing endoplasmic reticulum (ER) plays an mitochondrial intermembrane space detailed insights into the mechanics of active role in defining the sites of into the cytosol to trigger apoptosis, mitochondrial division, two major mitochondrial division and thereby and it is thought to facilitate the questions remained unanswered. First, helps to shape the mitochondrial removal of damaged organelles by Dnm1 was observed to assemble on compartment. autophagy [2]. Given this multitude of many sites on yeast mitochondria, but Mitochondria are highly dynamic cellular functions, it is not surprising not every Dnm1 oligomer was found to organelles that frequently fuse and that defects in mitochondrial fusion promote a mitochondrial fission event divide. This dynamic behaviour and fission are associated with several [10]. Thus, it is not known how the determines mitochondrial morphology diseases, including age-associated mitochondrial division sites are and serves many important functions neurodegeneration or neonatal selected from the Dnm1 assembly [2]. The formation of large, death [2]. sites. And second, the diameter of interconnected mitochondrial The key protein mediating Dnm1 helices assembled on lipid tubes networks by the fusion of individual mitochondrial division is an in vitro (w100 nm) is much smaller than organelles facilitates the transmission evolutionarily conserved the diameter of a typical mitochondrial of the mitochondrial membrane dynamin-related protein called Dnm1 in tubule (w300 nm) [6]. So how can Dispatch R923 a narrow Dnm1 helix assemble on proteins are absent. Furthermore, it a rather thick mitochondrion? The was shown previously that disruption ER study by Friedman et al. [1] may hold of Drp1 function severely disturbs answers to both of these questions. morphology and distribution of the ER Dynamin-related A number of studies have revealed in mammalian cells [14]. Hence, the protein close contacts between the ER and membrane-shaping activities of the ER mitochondria by light and electron and mitochondria may be mutually microscopy [11,12]. Now, Friedman beneficial for both organelles. et al. [1] analyzed the What are the proteins that establish three-dimensional structure of the ER–mitochondria contacts at future contacts between mitochondria and fission sites? The answer to this Mitochondrion ER by electron tomography in yeast question is not known, but previously Current Biology cells. They observed that ER tubules described organelle-bridging proteins occasionally were wrapped around [15] are prime candidates. In yeast, Figure 1. ER-mediated constriction of mito- mitochondria, and in some instances a mitochondria–ER tethering complex chondrial division sites. almost completely circumscribed the was recently identified that is ER and mitochondria are frequently present mitochondrial surface. Intriguingly, the composed of subunits resident in both in close apposition. Membrane contact sites are thought to play important roles in the mitochondrial diameter was the ER and mitochondria. As this exchange of membrane lipids and calcium substantially reduced at the ER contact complex is localized at discrete foci at signalling [15]. Friedman et al. [1] identified domains, suggesting a potential role in sites of close apposition between ER a new type of ER–mitochondrial interface. mitochondrial constriction and/or and mitochondria, it was termed the ER tubules are wrapped around mitochon- division. By time-resolved live-cell ER–mitochondria encounter structure dria, sometimes almost completely circum- fluorescence microscopy the authors (ERMES) [16]. The fact that deletion of scribing the mitochondrial outer membrane. The diameter of mitochondrial tubules is observed that most of the any of its subunits results in severe significantly reduced at these sites, allowing mitochondrial division events indeed mitochondrial morphology defects [17] the assembly of relatively narrow spirals of occurred at ER contact sites, both in is compatible with a role for ERMES in dynamin-related protein oligomers that drive yeast and in mammalian cells. determining sites of mitochondrial mitochondrial division. Consistent with this observation, fission. Homologous genes encoding GFP-tagged Dnm1 or Drp1 was found ERMES subunits in mammals are as yet to assemble on mitochondria unknown. However, physical linkages mitochondrial fission? What are the preferentially at sites of of ER and mitochondria were found by physiological consequences of mitochondrial–ER contact. As shown in electron tomography [18] and disrupting or enhancing mitochondrial RNAi-treated mammalian cells,