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Review
. 2018 Aug;470(8):1181-1192.
doi: 10.1007/s00424-018-2179-z. Epub 2018 Jul 7.

Mitochondrial junctions with cellular organelles: Ca2+ signalling perspective

Affiliations
Review

Mitochondrial junctions with cellular organelles: Ca2+ signalling perspective

Alexei V Tepikin. Pflugers Arch. 2018 Aug.

Abstract

Cellular organelles form multiple junctional complexes with one another and the emerging research area dealing with such structures and their functions is undergoing explosive growth. A new research journal named "Contact" has been recently established to facilitate the development of this research field. The current consensus is to define an organellar junction by the maximal distance between the participating organelles; and the gap of 30 nm or less is considered appropriate for classifying such structures as junctions or membrane contact sites. Ideally, the organellar junction should have a functional significance, i.e. facilitate transfer of calcium, sterols, phospholipids, iron and possibly other substances between the organelles (Carrasco and Meyer in Annu Rev Biochem 80:973-1000, 2011; Csordas et al. in Trends Cell Biol 28:523-540, 2018; Phillips and Voeltz in Nat Rev Mol Cell Biol 17:69-82, 2016; Prinz in J Cell Biol 205:759-769, 2014). It is also important to note that the junction is not just a result of a random organelle collision but have active and specific formation, stabilisation and disassembly mechanisms. The nature of these mechanisms and their role in physiology/pathophysiology are the main focus of an emerging research field. In this review, we will briefly describe junctional complexes formed by cellular organelles and then focus on the junctional complexes that are formed by mitochondria with other organelles and the role of these complexes in regulating Ca2+ signalling.

Keywords: Ca2+ signalling; Endoplasmic reticulum; Membrane contact sites; Mitochondria; Organellar junctions; Reactive oxygen species.

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Figures

Fig. 1
Fig. 1
Mitochondrial junctions/interactions with other cellular organelles. Abbreviations in this figure: plasma membrane (PM), endoplasmic reticulum (ER), smooth ER (SER); rough ER (RER); lipid droplet (LD); peroxisome (PRX); endosomes/lysosomes (E/L); Golgi (G). The tethers linking the organelles are indicated by short black bars. Two types of mitochondrial junctions with the SER are included in the figure. The lower mitochondrial-SER junction (SER strand approaches perpendicularly to the mitochondrial outer membrane) illustrates the interaction involved in mitochondrial fission [20, 50, 90]). The upper mitochondrial-SER junction (membranes of the organelles are running parallel to one another) is involved in signalling and lipid transfer between the organelles but not in mitochondrial fission. Note the difference in the length of the tethers between the mitochondrial-SER junctions and mitochondrial-RER junctions (see [29]). A number of triple organellar junctions have been reported (e.g. [159]); in this diagram, we show a putative triple mitochondria-PM-ER junction. Two or three types of tethers could be formed in the triple junctions (two types is the minimal requirement); in this diagram, we show the three types of tethers for illustrative purposes. The strand of ER approaching the PM in the proximity of the ER-PM junction could be SEM [126] or REM [106] but only ribosome-free ER membranes have been shown to form junctions with PM [106, 126]. The properties of the ER and PM in the triple contact regions with mitochondria require further investigations
Fig. 2
Fig. 2
Mitochondria can be found in close proximity to the endoplasmic reticulum and the plasma membrane in pancreatic acinar cells. a Images of mitochondria in live pancreatic acinar cells (adapted with modifications from [165]). Mitochondria were loaded with the ΔΨ indicator TMRM (tetramethylrhodamine methyl ester). SP-M indicates subplasmalemmal mitochondria (see also parts c and d of this figure and [76, 129]). PG-M indicates perigranular mitochondria. In this cell type, PG-M can be found in close proximity to Golgi, ER strands and secretory granules (see [38, 76, 129, 158]). Scale bar corresponds to 4 μm. b Example a mitochondrion located in a close proximity to a rough ER strand (adapted with modifications from [76]). Ri indicates ribosome. ER-L indicates the ER lumen. Scale bar represents 100 nm. c ER-PM junctions (indicated by arrowheads) with associated mitochondrion (m). The image is adapted with modifications from [106]). The lumens of ER strands approaching the plasma membranes are highlighted by asterisks. This image is an example of a triple organellar junction in a primary mammalian cell. Scale bar represents approximately 50 nm. d Subplasmalemmal mitochondrion (SP-M) shown with associated plasma membrane (PM) region. Note the strands of the rough ER in close proximity to the mitochondrion on the other side from the PM. Scale bar corresponds to approximately 100 nm. The figure was adapted with modifications from [76]

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