Interacting organelles

Abstract

Eukaryotic cells are organized into membrane-bound organelles. These organelles communicate with one another through vesicular trafficking pathways and membrane contact sites (MCSs). MCSs are sites of close apposition between two or more organelles that play diverse roles in the exchange of metabolites, lipids and proteins. Organelle interactions at MCSs also are important for organelle division and biogenesis. For example, the division of several organelles, including mitochondria and endosomes, seem to be regulated by contacts with the endoplasmic reticulum (ER). Moreover, the biogenesis of autophagosomes and peroxisomes involves contributions from the ER and multiple other cellular compartments. Thus, organelle-organelle interactions allow cells to alter the shape and activities of their membrane-bound compartments, allowing them to cope with different developmental and environmental conditions.

Figure 1:. Functions of organelle contacts.

Shown are contacts between organelles where at least one protein involved in mediating the contact has been identified. ER-lysosome and ER-endosome contacts play roles in lipid exchange, Ca²⁺ dynamics, and organelle fission [3]. Lysosomes also play a role in mitochondrial fission, at lysosome-mitochondria-ER contact sites [37]. ER-plasma membrane (PM) contact sites are involved in lipid and Ca²⁺ exchange [3,4]. All the other shown organelle contacts have proposed lipid exchange functions [3,23,29,71]. Finally, ER-LD contacts also allow proteins to transfer between these organelles [26,28].

Figure 2:. Mitochondrial constriction at ER-mitochondria contact sites.

An example of organelle interactions regulating organelle division. Spire1C:actin complexes on mitochondria associate with inverted formin 2 (INF2) on the ER. Actin filaments nucleated by Spire1C are elongated by the actin polymerization activity of INF2. The actin filament elongation activity exerts pressure on the mitochondrial outer membrane, thereby driving constriction of the latter. Tethering complexes may play a role in maintaining association between ER and mitochondrial membranes. Modified with permission from [35].

Figure 3:. FIB-SEM showing ER-organelle contacts in a neuron.

3-dimensional model of subcellular organelles from a FIB-SEM image stack of a dendritic segment within a neuron of the nucleus accumbens brain region. Membrane areas in contact with the ER are shown in dark red. Scale bar, 1.6 μm. Figure courtesy of Pietro de Camilli.

Figure 4:. Organelle organization and contacts revealed by multispectral lattice light sheet microscopy.

(a) Maximum intensity projection of a COS-7 cell expressing fluorescent proteins targeted to peroxisomes, the mitochondria, the ER, and the Golgi, and labelled with dyes to mark lysosomes and LDs. (b) Examples of complex interorganelle contacts and organization in segmented lattice light sheet images. The ER is excluded for clarity. (c) Dynamics of mitochondria-organelle interactions in segmented lattice light sheet images. Mitochondria are shown in grey, while contacts between mitochondria and other organelles are colored according to the legend. Numbers represent time in seconds. (b) is modified with permission from [5].