Mitochondrial phosphatase PTPMT1 is essential for cardiolipin biosynthesis.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, J; Guan, Z; Murphy, AN; Wiley, SE; Perkins, GA; Worby, CA; Engel, JL; Heacock, P; Nguyen, OK; Wang, JH; Raetz, CRH; Dowhan, W; Dixon, JE

Published Date

  • June 8, 2011

Published In

Volume / Issue

  • 13 / 6

Start / End Page

  • 690 - 700

PubMed ID

  • 21641550

Pubmed Central ID

  • 21641550

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2011.04.007

Language

  • eng

Conference Location

  • United States