Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic beta cells

Mol Cell. 2005 Jul 22;19(2):197-207. doi: 10.1016/j.molcel.2005.06.008.


Reversible phosphorylation is the cell's most prevalent form of posttranslational modification, yet its role in the regulation of mitochondrial functions is poorly understood. We have discovered that a member of the dual-specific protein tyrosine phosphatase (DS-PTP) family, PTPMT1 (PTP localized to the Mitochondrion 1) resides nearly exclusively in mitochondria. PTPMT1 is targeted to the mitochondrion by an N-terminal signal sequence and is found anchored to the matrix face of the inner membrane. Knockdown of PTPMT1 expression in the pancreatic insulinoma cell line INS-1 832/13 alters the mitochondrial phosphoprotein profile and markedly enhances both ATP production and insulin secretion. These data define PTPMT1 as a potential drug target for the treatment of type II diabetes and strengthen the notion that mitochondria are an underappreciated site of signaling by reversible phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / biosynthesis*
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / cytology
  • Islets of Langerhans / enzymology
  • Islets of Langerhans / metabolism*
  • Mice
  • Mitochondria / enzymology*
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Protein Tyrosine Phosphatases / metabolism*
  • Time Factors


  • Insulin
  • Adenosine Triphosphate
  • Protein Tyrosine Phosphatases