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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Pagliarini, DJ; Wiley, SE; Kimple, ME; Dixon, JR; Kelly, P; Worby, CA; Casey, PJ; Dixon, JE

Published Date

  • July 22, 2005

Published In

Volume / Issue

  • 19 / 2

Start / End Page

  • 197 - 207

PubMed ID

  • 16039589

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2005.06.008


  • eng

Conference Location

  • United States