{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Guna A"],"funding":["Howard Hughes Medical Institute","NHGRI NIH HHS","NINDS NIH HHS"],"pagination":["317-322"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9674023"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["378(6617)"],"pubmed_abstract":["In the mitochondrial outer membrane, α-helical transmembrane proteins play critical roles in cytoplasmic-mitochondrial communication. Using genome-wide CRISPR screens, we identified mitochondrial carrier homolog 2 (MTCH2), and its paralog MTCH1, and showed that it is required for insertion of biophysically diverse tail-anchored (TA), signal-anchored, and multipass proteins, but not outer membrane β-barrel proteins. Purified MTCH2 was sufficient to mediate insertion into reconstituted proteoliposomes. Functional and mutational studies suggested that MTCH2 has evolved from a solute carrier transporter. MTCH2 uses membrane-embedded hydrophilic residues to function as a gatekeeper for the outer membrane, controlling mislocalization of TAs into the endoplasmic reticulum and modulating the sensi"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["MTCH2 is a mitochondrial outer membrane protein insertase."],"pmcid":["PMC9674023"],"funding_grant_id":["F31 NS115380","RM1 HG009490"],"pubmed_authors":["Shaffer KCL","Replogle JM","Muthukumar G","Jones JJ","Weissman JS","Chou TF","Guna A","Stevens TA","Pogson AN","Esantsi TK","Voorhees RM","Lomenick B","Inglis AJ","Wang ML"],"additional_accession":[]},"is_claimable":false,"name":"MTCH2 is a mitochondrial outer membrane protein insertase.","description":"In the mitochondrial outer membrane, α-helical transmembrane proteins play critical roles in cytoplasmic-mitochondrial communication. Using genome-wide CRISPR screens, we identified mitochondrial carrier homolog 2 (MTCH2), and its paralog MTCH1, and showed that it is required for insertion of biophysically diverse tail-anchored (TA), signal-anchored, and multipass proteins, but not outer membrane β-barrel proteins. Purified MTCH2 was sufficient to mediate insertion into reconstituted proteoliposomes. Functional and mutational studies suggested that MTCH2 has evolved from a solute carrier transporter. MTCH2 uses membrane-embedded hydrophilic residues to function as a gatekeeper for the outer membrane, controlling mislocalization of TAs into the endoplasmic reticulum and modulating the sensi","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2025-04-25T21:04:44.54Z","creation":"2025-04-06T08:35:08.465Z"},"accession":"S-EPMC9674023","cross_references":{"pubmed":["36264797"],"doi":["10.1126/science.add1856"]}}