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Mitochondrial phosphatase PTPMT1 is essential for cardiolipin biosynthesis.

Cell metabolism | 2011

PTPMT1 was the first protein tyrosine phosphatase found localized to the mitochondria, but its biological function was unknown. Herein, we demonstrate that whole body deletion of Ptpmt1 in mice leads to embryonic lethality, suggesting an indispensable role for PTPMT1 during development. Ptpmt1 deficiency in mouse embryonic fibroblasts compromises mitochondrial respiration and results in abnormal mitochondrial morphology. Lipid analysis of Ptpmt1-deficient fibroblasts reveals an accumulation of phosphatidylglycerophosphate (PGP) along with a concomitant decrease in phosphatidylglycerol. PGP is an essential intermediate in the biosynthetic pathway of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle. We further demonstrate that PTPMT1 specifically dephosphorylates PGP in vitro. Loss of PTPMT1 leads to dramatic diminution of cardiolipin, which can be partially reversed by the expression of catalytic active PTPMT1. Our study identifies PTPMT1 as the mammalian PGP phosphatase and points to its role as a regulator of cardiolipin biosynthesis.

Pubmed ID: 21641550 RIS Download

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: GM069338
  • Agency: NIDDK NIH HHS, United States
    Id: P01 DK054441
  • Agency: NIDDK NIH HHS, United States
    Id: R37 DK018024-31
  • Agency: NCRR NIH HHS, United States
    Id: P41 RR004050
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM056389
  • Agency: NIGMS NIH HHS, United States
    Id: GM56389
  • Agency: NIDDK NIH HHS, United States
    Id: R37 DK018024
  • Agency: NIDDK NIH HHS, United States
    Id: DK18024
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM056389-05
  • Agency: NCRR NIH HHS, United States
    Id: P41 RR004050-16
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK018024
  • Agency: NIDDK NIH HHS, United States
    Id: DK054441
  • Agency: NIGMS NIH HHS, United States
    Id: U54 GM069338-07
  • Agency: NIGMS NIH HHS, United States
    Id: U54 GM069338
  • Agency: NCRR NIH HHS, United States
    Id: RR04050
  • Agency: NIDDK NIH HHS, United States
    Id: P01 DK054441-04
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK018849-31
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK018849
  • Agency: NIDDK NIH HHS, United States
    Id: DK18849

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