Acylglycerol Kinase Mutated in Sengers Syndrome Is a Subunit of the TIM22 Protein Translocase in Mitochondria

Milena Vukotic, Hendrik Nolte, Tim König, Shotaro Saita, Maria Ananjew, Marcus Krüger, Takashi Tatsuta, Thomas Langer

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


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.

Original languageEnglish
Pages (from-to)471-483.e7
JournalMolecular Cell
Issue number3
StatePublished - 3 Aug 2017
Externally publishedYes


  • Sengers syndrome
  • TIM22 complex
  • acylglycerol kinase
  • apoptosis
  • cardiolipin
  • cristae
  • mitochondria
  • mitochondrial protein import
  • phosphatidic acid


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