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

David J. Pagliarini, Sandra E. Wiley, Michelle E. Kimple, Jesse R. Dixon, Patrick Kelly, Carolyn A. Worby, Patrick J. Casey, Jack E. Dixon

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)197-207
Number of pages11
JournalMolecular cell
Volume19
Issue number2
DOIs
StatePublished - Jul 22 2005

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