Vukotic, Milena, Nolte, Hendrik, Koenig, Tim, Saita, Shotaro ORCID: 0000-0002-7406-8361, Ananjew, Maria, Krueger, Marcus, 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:
CreatorsEmailORCIDORCID Put Code
Vukotic, MilenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenig, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saita, ShotaroUNSPECIFIEDorcid.org/0000-0002-7406-8361UNSPECIFIED
Ananjew, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tatsuta, TakashiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
X-LINKED GENE; INTRAMITOCHONDRIAL TRANSPORT; MEDIATES INSERTION; COMPLEX; IDENTIFICATION; ORGANIZATION; PATHWAY; DNAJC19; IMPORT; CANCERMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22197

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