TY  - INPR
A1  - Naha, Ritam
A1  - Strohm, Rebecca
A1  - Urbach, Jennifer
A1  - Wittig, Ilka
A1  - Reichert, Andreas
A1  - Kondadi, Arun Kumar
A1  - Anand, Ruchika
T1  - SLP2 coordinates MICOS assembly and cristae morphogenesis via MIC13 and YME1L
T2  - bioRxiv
N2  - The MICOS complex subunit MIC13 is essential for mitochondrial cristae organization. Mutations in MIC13 cause severe mitochondrial hepato-encephalopathy displaying defective cristae morphology and loss of the MIC10-subcomplex. Here we identified SLP2 as a novel interacting partner of MIC13 and decipher a critical role of SLP2 for MICOS assembly at distinct steps. SLP2 provides a large interaction hub for MICOS subunits and loss of SLP2 imparted YME1L-mediated proteolysis of MIC26 and drastic alterations in cristae morphology. We further identified a MIC13-specific role in stabilizing the MIC10-subcomplex via a MIC13-YME1L axis. SLP2 together with the stabilized MIC10-subcomplex promotes efficient assembly of the MIC60-subcomplex forming the MICOS-MIB complex. Consistently, super-resolution nanoscopy showed a dispersed distribution of the MIC60 in cells lacking SLP2 and MIC13. Our study reveals converging and interdependent assembly pathways for the MIC10- and MIC60-subcomplexes which are controlled in two ways, the MIC13-YME1L and the SLP2-YME1L axes, revealing mechanistic insights of these factors in cristae morphogenesis. These results will be helpful in understanding the human pathophysiology linked to mutations in MIC13 or its interaction partners.
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75439
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-754394
UR  - https://www.biorxiv.org/content/10.1101/2023.09.04.556207v1
IS  - 2023.09.04.556207, Version 1
ER  -