SLP2 and MIC13 Synergistically Coordinate MICOS Assembly and Crista Junction Formation

Overview

Journal iScience

Publisher Cell Press

Date 2024 Dec 25

PMID 39720525

Authors

Ritam Naha

Rebecca Strohm

Yulia Schaumkessel

Jennifer Urbach

Ilka Wittig

Andreas S Reichert

Arun Kumar Kondadi

Ruchika Anand

Affiliations

Soon will be listed here.

Abstract

The MICOS complex, essential for cristae organization, comprises MIC10 and MIC60 subcomplexes, with MIC13 as a crucial subunit. mutations cause severe mitochondrial hepato-encephalopathy, cristae defects, and MIC10-subcomplex loss. We demonstrate that depletion of the mitochondrial protease YME1L in KO stabilizes MIC10-subcomplex, restoring MIC60-MIC10 interaction and crista junction (CJ) defects, indicating MIC13 is crucial for MIC10-subcomplex stabilization rather than MIC60-MIC10 bridging. We identified stomatin-like protein 2 (SLP2) as a key MIC13 interaction partner, essential for cristae morphology and CJ formation. SLP2 serves as an interaction hub for MICOS subunits and stabilizes MIC26 by protecting it from YME1L-mediated degradation. Deleting both and impairs MIC60-subcomplex assembly and its nanoscale organization. Restoring the MIC10-subcomplex in double KO cells through YME1L depletion reinstates MIC60-subcomplex assembly and cristae morphology. Overall, we propose SLP2 and the MIC10-subcomplex act as a proteolytically controlled 'seeder' complex, facilitating MICOS-MIB complex assembly and maintaining mitochondrial integrity.

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