Identification of TMEM126A as OXA1L-interacting protein reveals cotranslational quality control in mitochondria

2023-12-29 | journal article

Jump to:Cite & Linked | Documents & Media | Details | Version history

Cite this publication

​Identification of TMEM126A as OXA1L-interacting protein reveals cotranslational quality control in mitochondria​
Poerschke, S.; Oeljeklaus, S.; Cruz-Zaragoza, L. D.; Schenzielorz, A.; Dahal, D.; Hillen, H. S. & Das, H. et al.​ (2023) 
Molecular Cell,.​ DOI: 

Documents & Media


GRO License GRO License


Poerschke, Sabine; Oeljeklaus, Silke; Cruz-Zaragoza, Luis Daniel; Schenzielorz, Alexander; Dahal, Drishan; Hillen, Hauke Sven; Das, Hirak; Kremer, Laura Sophie; Valpadashi, Anusha; Breuer, Mirjam; Sattmann, Johannes; Richter-Dennerlein, Ricarda ; Warscheid, Bettina; Dennerlein, Sven; Rehling, Peter
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.
Issue Date
Molecular Cell 
EXC 2067: Multiscale Bioimaging 
SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente 
SFB 1190 | P13: Protein Transport über den mitochondrialen Carrier Transportweg 
SFB 1190 | P23: Strukturelle Grundlagen des Proteintransports über die äußere mitochondriale Membran humaner Mitochondrien 
FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala 
FOR 2848 | P04: Analyse der räumlichen Organisation der OXPHOS Assemblierung in Säugerzellen 
FOR 2848 | St01: Structure and distribution of ribosomes at the inner mitochondrial membrane 
Working Group
RG Hillen (Structure and Function of Molecular Machines) 
RG Rehling (Mitochondrial Protein Biogenesis) 
RG Richter-Dennerlein (Mitoribosome Assembly) 
External URL



Social Media