Universität zu Köln

Zarges, Christine, Fieler, Hanna, Rothemann, Robin Alexander ORCID: 0000-0002-9502-5360, Poepsel, Simon, Jae, Lucas T. ORCID: 0000-0002-3531-1760 and Riemer, Jan ORCID: 0000-0002-7574-8457 (2025). The mitochondrial disulphide relay substrate FAM136A safeguards IMS proteostasis and cellular fitness. Redox Biology, 87. pp. 1-17. Elsevier. ISSN 2213-2317

PDF 1-s2.0-S2213231725003970-main.pdf Bereitstellung unter der CC-Lizenz: Creative Commons Attribution. Download (17MB)

Abstract

[Artikel-Nr.: 103884] The mitochondrial disulphide relay is the key machinery for import and oxidative protein folding in the mito- chondrial intermembrane space. Among IMS proteins with unknown function, we identified FAM136A as a new substrate of the mitochondrial disulphide relay. We demonstrate a transient interaction between FAM136A and MIA40, and that MIA40 introduces four disulphide bonds in two twin-CX3C motifs of FAM136A. Consequently, IMS import of FAM136A requires these cysteines and its steady state levels in intact cells are strongly dependent on MIA40 and AIFM1 levels. Furthermore, we show that FAM136A forms non-covalent homodimers as a mature protein. Acute deletion of FAM136A curtails cellular proliferation capacity and elicits a robust induction of the integrated stress response, coincident with the aggregation and/or depletion of selected IMS proteins including HAX1 and CLPB. Together, this establishes FAM136A as a pivotal component of the IMS proteostasis network, with implications for overall cellular function and health.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Zarges, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Fieler, Hanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Rothemann, Robin Alexander UNSPECIFIED https://orcid.org/0000-0002-9502-5360 UNSPECIFIED Poepsel, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Jae, Lucas T. UNSPECIFIED https://orcid.org/0000-0002-3531-1760 UNSPECIFIED Riemer, Jan UNSPECIFIED https://orcid.org/0000-0002-7574-8457 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-811169
Identification Number:	10.1016/j.redox.2025.103884
Journal or Publication Title:	Redox Biology
Volume:	87
Page Range:	pp. 1-17
Number of Pages:	17
Date:	November 2025
Publisher:	Elsevier
ISSN:	2213-2317
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases
Subjects:	Life sciences
Uncontrolled Keywords:	Keywords Language Oxidative protein folding ; FAM136A ; MIA40 ; Integrated stress response English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81116