Universität zu Köln

Vukotic, Milena, Nolte, Hendrik, Koenig, Tim, Saita, Shotaro ORCID: 0000-0002-7406-8361, Ananjew, Maria, Krueger, Marcus ORCID: 0000-0003-2008-4582, Tatsuta, Takashi and Langer, Thomas (2017). Acylglycerol Kinase Mutated in Sengers Syndrome Is a Subunit of the TIM22 Protein Translocase in Mitochondria. Mol. Cell, 67 (3). S. 471 - 491. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

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Abstract

Mutations in mitochondrial acylglycerol kinase (AGK) cause Sengers syndrome, which is characterized by cataracts, hypertrophic cardiomyopathy, and skeletal myopathy. AGK generates phosphatidic acid and lysophosphatidic acid, bioactive phospholipids involved in lipid signaling and the regulation of tumor progression. However, the molecular mechanisms of the mitochondrial pathology remain enigmatic. Determining its mitochondrial interactome, we have identified AGK as a constituent of the TIM22 complex in the mitochondrial inner membrane. AGK assembles with TIMM22 and TIMM29 and supports the import of a subset of multi-spanning membrane proteins. The function of AGK as a subunit of the TIM22 complex does not depend on its kinase activity. However, enzymatically active AGK is required to maintain mitochondrial cristae morphogenesis and the apoptotic resistance of cells. The dual function of AGK as lipid kinase and constituent of the TIM22 complex reveals that disturbances in both phospholipid metabolism and mitochondrial protein biogenesis contribute to the pathogenesis of Sengers syndrome.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vukotic, Milena UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Koenig, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Saita, Shotaro UNSPECIFIED orcid.org/0000-0002-7406-8361 UNSPECIFIED Ananjew, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Tatsuta, Takashi UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-221970
DOI:	10.1016/j.molcel.2017.06.013
Journal or Publication Title:	Mol. Cell
Volume:	67
Number:	3
Page Range:	S. 471 - 491
Date:	2017
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4164
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 X-LINKED GENE; INTRAMITOCHONDRIAL TRANSPORT; MEDIATES INSERTION; COMPLEX; IDENTIFICATION; ORGANIZATION; PATHWAY; DNAJC19; IMPORT; CANCER Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22197