Cellular proteostasis requires transport of polypeptides across membranes. Although defective transport processes trigger cytosolic rescue and quality control mechanisms that clear translocases and membranes from unproductive cargo, proteins that are synthesized within mitochondria are not accessible to these mechanisms. Mitochondrial-encoded proteins are inserted cotranslationally into the inner membrane by the conserved insertase OXA1L. Here, we identify TMEM126A as a OXA1L-interacting protein. TMEM126A associates with mitochondrial ribosomes and translation products. Loss of TMEM126A leads to the destabilization of mitochondrial translation products, triggering an inner membrane quality control process, in which newly synthesized proteins are degraded by the mitochondrial iAAA protease. Our data reveal that TMEM126A cooperates with OXA1L in protein insertion into the membrane. Upon loss of TMEM126A, the cargo-blocked OXA1L insertase complexes undergo proteolytic clearance by the iAAA protease machinery together with its cargo.
%0 Journal Article
%1 poerschkeIdentificationTMEM126AOXA1Linteracting2024a
%A Poerschke, Sabine
%A Oeljeklaus, Silke
%A Cruz-Zaragoza, Luis Daniel
%A Schenzielorz, Alexander
%A Dahal, Drishan
%A Hillen, Hauke Sven
%A Das, Hirak
%A Kremer, Laura Sophie
%A Valpadashi, Anusha
%A Breuer, Mirjam
%A Sattmann, Johannes
%A Richter-Dennerlein, Ricarda
%A Warscheid, Bettina
%A Dennerlein, Sven
%A Rehling, Peter
%C United States
%D 2024
%J Molecular cell
%K *Mitochondria/genetics/metabolism,*Mitochondrial Biosynthesis,Ribosomes/metabolism,to_read Hydrolases/metabolism,Protein Membranes/metabolism,mitochondria,Mitochondrial Proteins/metabolism,mitochondrial control,mitochondrial quality translation,Peptide
%N 2
%P 345-358.e5
%R 10.1016/j.molcel.2023.12.013
%T Identification of TMEM126A as OXA1L-interacting Protein Reveals Cotranslational Quality Control in Mitochondria.
%V 84
%X Cellular proteostasis requires transport of polypeptides across membranes. Although defective transport processes trigger cytosolic rescue and quality control mechanisms that clear translocases and membranes from unproductive cargo, proteins that are synthesized within mitochondria are not accessible to these mechanisms. Mitochondrial-encoded proteins are inserted cotranslationally into the inner membrane by the conserved insertase OXA1L. Here, we identify TMEM126A as a OXA1L-interacting protein. TMEM126A associates with mitochondrial ribosomes and translation products. Loss of TMEM126A leads to the destabilization of mitochondrial translation products, triggering an inner membrane quality control process, in which newly synthesized proteins are degraded by the mitochondrial iAAA protease. Our data reveal that TMEM126A cooperates with OXA1L in protein insertion into the membrane. Upon loss of TMEM126A, the cargo-blocked OXA1L insertase complexes undergo proteolytic clearance by the iAAA protease machinery together with its cargo.
@article{poerschkeIdentificationTMEM126AOXA1Linteracting2024a,
abstract = {Cellular proteostasis requires transport of polypeptides across membranes. Although defective transport processes trigger cytosolic rescue and quality control mechanisms that clear translocases and membranes from unproductive cargo, proteins that are synthesized within mitochondria are not accessible to these mechanisms. Mitochondrial-encoded proteins are inserted cotranslationally into the inner membrane by the conserved insertase OXA1L. Here, we identify TMEM126A as a OXA1L-interacting protein. TMEM126A associates with mitochondrial ribosomes and translation products. Loss of TMEM126A leads to the destabilization of mitochondrial translation products, triggering an inner membrane quality control process, in which newly synthesized proteins are degraded by the mitochondrial iAAA protease. Our data reveal that TMEM126A cooperates with OXA1L in protein insertion into the membrane. Upon loss of TMEM126A, the cargo-blocked OXA1L insertase complexes undergo proteolytic clearance by the iAAA protease machinery together with its cargo.},
added-at = {2024-05-17T13:01:35.000+0200},
address = {United States},
author = {Poerschke, Sabine and Oeljeklaus, Silke and {Cruz-Zaragoza}, Luis Daniel and Schenzielorz, Alexander and Dahal, Drishan and Hillen, Hauke Sven and Das, Hirak and Kremer, Laura Sophie and Valpadashi, Anusha and Breuer, Mirjam and Sattmann, Johannes and {Richter-Dennerlein}, Ricarda and Warscheid, Bettina and Dennerlein, Sven and Rehling, Peter},
biburl = {https://www.bibsonomy.org/bibtex/2542c2b1a8dec191785622496732a4566/warscheidlab},
copyright = {Copyright {\copyright} 2023 The Author(s). Published by Elsevier Inc. All rights reserved.},
doi = {10.1016/j.molcel.2023.12.013},
interhash = {2b3c9dcb60f9593294a273f8a3684558},
intrahash = {542c2b1a8dec191785622496732a4566},
issn = {1097-4164 1097-2765},
journal = {Molecular cell},
keywords = {*Mitochondria/genetics/metabolism,*Mitochondrial Biosynthesis,Ribosomes/metabolism,to_read Hydrolases/metabolism,Protein Membranes/metabolism,mitochondria,Mitochondrial Proteins/metabolism,mitochondrial control,mitochondrial quality translation,Peptide},
langid = {english},
month = jan,
number = 2,
pages = {345-358.e5},
pmcid = {PMC10805001},
pmid = {38199007},
timestamp = {2024-05-17T13:01:35.000+0200},
title = {Identification of {{TMEM126A}} as {{OXA1L-interacting}} Protein Reveals Cotranslational Quality Control in Mitochondria.},
volume = 84,
year = 2024
}