MTCH2 is a mitochondrial outer membrane protein insertase.
Science
; 378(6617): 317-322, 2022 10 21.
Article
en En
| MEDLINE
| ID: mdl-36264797
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 ß-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 sensitivity of leukemia cells to apoptosis. Our identification of MTCH2 as an insertase provides a mechanistic explanation for the diverse phenotypes and disease states associated with MTCH2 dysfunction.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Apoptosis
/
Proteínas de Transporte de Membrana Mitocondrial
/
Membranas Mitocondriales
Límite:
Humans
Idioma:
En
Revista:
Science
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos