Wai, Timothy ORCID: 0000-0002-6770-6222, Saita, Shotaro ORCID: 0000-0002-7406-8361, Nolte, Hendrik, Mueller, Sebastian, Koenig, Tim, Richter-Dennerlein, Ricarda, Sprenger, Hans-Georg, Madrenas, Joaquin, Muehlmeister, Mareike, Brandt, Ulrich ORCID: 0000-0003-1869-6811, Krueger, Marcus and Langer, Thomas (2016). The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the i-AAA protease YME1L. EMBO Rep., 17 (12). S. 1844 - 1857. HOBOKEN: WILEY. ISSN 1469-3178

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wai, TimothyUNSPECIFIEDorcid.org/0000-0002-6770-6222UNSPECIFIED
Saita, ShotaroUNSPECIFIEDorcid.org/0000-0002-7406-8361UNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenig, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richter-Dennerlein, RicardaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sprenger, Hans-GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madrenas, JoaquinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muehlmeister, MareikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brandt, UlrichUNSPECIFIEDorcid.org/0000-0003-1869-6811UNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-254742
DOI: 10.15252/embr.201642698
Journal or Publication Title: EMBO Rep.
Volume: 17
Number: 12
Page Range: S. 1844 - 1857
Date: 2016
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1469-3178
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
STOMATIN-LIKE PROTEIN-2; INNER-MEMBRANE; OMA1; PROHIBITINS; OPA1; CRISTAE; COMPLEX; DEGRADATION; APOPTOSIS; IDENTIFICATIONMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/25474

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