Figure 5.

Roles of mitochondria-ER contacts. The physical contacts established between mitochondria and ER are responsible for several cellular processes such as mitochondrial fission, calcium buffering, and phospholipid synthesis. During mitochondrial fission, ER tubules are found in contact with mitochondria in the future fission sites. Drp1 is recruited to these sites and, together with ER tubules, promotes constriction and fission of mitochondria. Calcium (Ca²⁺) is transported from the ER to mitochondria via transporters in each membrane. On the ER membrane, Ca²⁺ is exported via the inositol 1,4,5-triphosphate receptor (I3PR) to the voltage-dependent anion-selective channel (VDAC) on the mitochondrial outer membrane. For the synthesis of some phospholipids, the required enzymes are found in the mitochondria and not in the endoplasmic reticulum (ER). This implies the transfer of precursor forms of phospholipids from the ER to mitochondria where they can be modified and then re-transferred to the ER. For example, the production of the mitochondrial phospholipid cardiolipin (CL) depends on precursor lipids present at the ER. Phosphatidic acid (PA) is transferred from the ER, across the IMS to the IMM, where it is enzymatically modified to form CL, which is further transported to the OMM. An example of a bidirectional movement of lipids between the ER and mitochondria is the production of phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Phosphatidylserine (PS) is first produced on the ER membrane and then translocated to the OMM. On the OMM, PS is transferred to the IMM where it is enzymatically modified to form PE. Finally, in order to produce PC, the precursor PE must be transferred back to the ER where specific enzymes modify it into PC.