Figure 1.

Cancer-relevant interactions between mitochondria and the ER at mito–ER contact sites (MERCs). Calcium transfer from the ER to mitochondria through the IP3R–GRP75–VDAC complex modulates mitochondrial energy metabolism and apoptosis induction, and is regulated by post-translational modifications of IP3R, ROS and associations with proteins such as TG2 and BRCA1. Further, proteins such as IRE1α and the Sig1R-BiP complex can interfere with the calcium transfer. Mitochondrial ATP, on the other hand, is important for the correct functioning of SERCA, and thus ER calcium homeostasis. These mechanisms influence, amongst others, cancer cell proliferation, invasion, cell death and mitochondrial dynamics. In addition to calcium, lipid homeostasis is also regulated at MERCs. MFN2 is important for the transfer of phosphatidylserine (PS) from the ER to mitochondria, where it is converted to phosphatidylethanolammine (PE), while the MAM-resident protein ACAT1 converts cholesterol to ceramide, a sphingolipid often abundantly found in cancer. Impaired lipid homeostasis has been associated with different kinds of tumors, such as liver, breast, pancreatic and colon cancers. For abbreviations, please refer to the text. This figure was created using images from Servier Medical Art (http://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License.