Universität zu Köln

Saita, Shotaro ORCID: 0000-0002-7406-8361, Tatsuta, Takashi, Lampe, Philipp A., Koenig, Tim, Ohba, Yohsuke and Langer, Thomas (2018). PARL partitions the lipid transfer protein STARD7 between the cytosol and mitochondria. Embo J., 37 (4). HOBOKEN: WILEY. ISSN 1460-2075

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Abstract

Intramembrane-cleaving peptidases of the rhomboid family regulate diverse cellular processes that are critical for development and cell survival. The function of the rhomboid protease PARL in the mitochondrial inner membrane has been linked to mitophagy and apoptosis, but other regulatory functions are likely to exist. Here, we identify the START domain-containing protein STARD7 as an intramitochondrial lipid transfer protein for phosphatidylcholine. We demonstrate that PARL-mediated cleavage during mitochondrial import partitions STARD7 to the cytosol and the mitochondrial intermembrane space. Negatively charged amino acids in STARD7 serve as a sorting signal allowing mitochondrial release of mature STARD7 upon cleavage by PARL. On the other hand, membrane insertion of STARD7 mediated by the TIM23 complex promotes mitochondrial localization of mature STARD7. Mitochondrial STARD7 is necessary and sufficient for the accumulation of phosphatidylcholine in the inner membrane and for the maintenance of respiration and cristae morphogenesis. Thus, PARL preserves mitochondrial membrane homeostasis via STARD7 processing and is emerging as a critical regulator of protein localization between mitochondria and the cytosol.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Saita, Shotaro UNSPECIFIED orcid.org/0000-0002-7406-8361 UNSPECIFIED Tatsuta, Takashi UNSPECIFIED UNSPECIFIED UNSPECIFIED Lampe, Philipp A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koenig, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Ohba, Yohsuke UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-195913
DOI:	10.15252/embj.201797909
Journal or Publication Title:	Embo J.
Volume:	37
Number:	4
Date:	2018
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1460-2075
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTRAMITOCHONDRIAL TRANSPORT; 3-METHYLGLUTACONIC ACIDURIA; PHOSPHATASE; MUTATIONS; CLPB; PHOSPHATIDYLCHOLINE; PINK1; PGAM5; NEUTROPENIA; DEFICIENCY Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19591