2.A.29.25.2
The mitochondrial carrier homologue-2 (MTCH2). Binds the BH3-interacting domain death agonist, BID. Regulated (induced) by the hepatocyte growth factor receptor, HGF/SF or Met. It has been proposed that its transport function has been lost (Robinson et al., 2012). Surprisingly, this protein has been reported to be targetted to the outer mitochondrial membrane (Gutiérrez-Aguilar and Baines, 2013).  MTCH2 is a mitochondrial outer membrane protein insertase (Guna et al. 2022). It is required for insertion of biophysically diverse tail-anchored (TA), signal-anchored, and multipass proteins, but not outer membrane beta-barrel proteins. Scramblases play a pivotal role in facilitating bidirectional lipid transport across cell membranes, thereby influencing lipid metabolism, membrane homeostasis, and cellular signaling (Bartoš et al. 2024). MTCH2, an insertase, has a membrane-spanning hydrophilic groove resembling those that form the lipid transit pathway in known scramblases. Bartoš et al. 2024 showed that MTCH2 reduces the free energy barrier for lipid movement along the groove and therefore can function as a scramblase. The scrambling rate of MTCH2 in silico is similar to that of voltage-dependent anion channel (VDAC), a recently discovered scramblase of the outer mitochondrial membrane, suggesting a potential complementary physiological role for these mitochondrial proteins. Other insertases which possess a hydrophilic path across the membrane like MTCH2, can also function as scramblases (Bartoš et al. 2024).