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EMBO Rep. 2016 Dec;17(12):1844-1856. Epub 2016 Oct 13.

The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the i-AAA protease YME1L.

Author information

1
Institute for Genetics Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), and University of Cologne, Cologne, Germany.
2
Microbiome and Disease Tolerance Centre, Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
3
Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
4
Institute for Genetics Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), and University of Cologne, Cologne, Germany thomas.langer@uni-koeln.de.
5
Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.

Abstract

The SPFH (stomatin, prohibitin, flotillin, HflC/K) superfamily is composed of scaffold proteins that form ring-like structures and locally specify the protein-lipid composition in a variety of cellular membranes. Stomatin-like protein 2 (SLP2) is a member of this superfamily that localizes to the mitochondrial inner membrane (IM) where it acts as a membrane organizer. Here, we report that SLP2 anchors a large protease complex composed of the rhomboid protease PARL and the i-AAA protease YME1L, which we term the SPY complex (for SLP2-PARL-YME1L). Association with SLP2 in the SPY complex regulates PARL-mediated processing of PTEN-induced kinase PINK1 and the phosphatase PGAM5 in mitochondria. Moreover, SLP2 inhibits the stress-activated peptidase OMA1, which can bind to SLP2 and cleaves PGAM5 in depolarized mitochondria. SLP2 restricts OMA1-mediated processing of the dynamin-like GTPase OPA1 allowing stress-induced mitochondrial hyperfusion under starvation conditions. Together, our results reveal an important role of SLP2 membrane scaffolds for the spatial organization of IM proteases regulating mitochondrial dynamics, quality control, and cell survival.

KEYWORDS:

OMA1; SLP2; YME1L; membrane scaffold; mitochondria; rhomboid

PMID:
27737933
PMCID:
PMC5283581
DOI:
10.15252/embr.201642698
[Indexed for MEDLINE]
Free PMC Article

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