Universität zu Köln

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 ORCID: 0000-0003-2008-4582 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:	Creators Email ORCID ORCID Put Code Wai, Timothy UNSPECIFIED orcid.org/0000-0002-6770-6222 UNSPECIFIED Saita, Shotaro UNSPECIFIED orcid.org/0000-0002-7406-8361 UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Koenig, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Richter-Dennerlein, Ricarda UNSPECIFIED UNSPECIFIED UNSPECIFIED Sprenger, Hans-Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Madrenas, Joaquin UNSPECIFIED UNSPECIFIED UNSPECIFIED Muehlmeister, Mareike UNSPECIFIED UNSPECIFIED UNSPECIFIED Brandt, Ulrich UNSPECIFIED orcid.org/0000-0003-1869-6811 UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Langer, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STOMATIN-LIKE PROTEIN-2; INNER-MEMBRANE; OMA1; PROHIBITINS; OPA1; CRISTAE; COMPLEX; DEGRADATION; APOPTOSIS; IDENTIFICATION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25474