**4. Structural link between ER and mitochondria**

The mitochondria consists of two membranes viz. an outer mitochondrial membrane (OMM) and inner mitochondrial membrane (IMM) which have several convoluted foldings called as cristae. The shape of mitochondria is very heterogeneous in living cells from sphere to interconnected tubules [20]. The formation of mitochondrial network is well documented by the continuous movements of mitochondria by motor proteins. During the mitochondrial movements rarely two mitochondria encounter each other to form fuse [20]. Sometimes the mitochondrial tubules can undergo fission to form two or more mitochondrial units. However, both mitochondrial processes are much complicated because of the coordination of fusion and fission of four lipid bilayers. The first mitochondrial fusion protein Fuzzy onions 1 protein (Fzolp) was identified in *Drosophila melanogaster* [21]. Later two Fzolp homologus mitofusin 1 (MFN1) and mitofusin 2 (MFN2) were identified from mammals [22]. The MFN1 and MFN2 have very high 81% homology and both are localized in the outer mitochondrial membrane [23]. These proteins are formed by the docking of two juxtaposed mitochondrial fusion through their transmembrane spanning region [24]. During the mitochondrial fission both Fis1 and dynamin-related protein1 (Drp1) play a vital role in mammals [25].

The endoplasmic reticulum is an extensive network of cisternae and microtubules and stretches from the nuclear envelop to the plasma membrane of all eukaryotic cells occupying 10% of the total cell volume [26]. The ribosomes bind to the peripheral of ER and to the nuclear envelope comprising the rough ER and ribosome-free is called as smooth ER. The peripheral ER consists of sheath-like cisternae and the thickness of the sheets and diameter of the tubules ranges from 60–100 nm. ER and microtubule associated proteins play a predominant role in shaping of mammalian cells [27]. The cytoskeleton membrane proteins 63 kDa (CLIMP63), VAP-B/Nir3 couple and p22 are involved with dynamics of ER and microtubule [28]. CLIMP63 is an integral peripheral ER membrane proteins which is anchoring of ER to microtubules and maintains the spatial distribution of ER network. The p22 has myristoylated EF-hand protein binds microtubule in a Ca2+ dependent manner and providing a link between ER morphology and Ca2+ [29]. The ER morphology is still controversial even though reticulons and DP1 proteins are enriched in ER tubule rather than sheets and nuclear envelope [30]. Another protein dynamin-related membrane GTPases atlastins are involved in the control of morphology of ER by promoting the branching of the tubules [31].
