Involvement of a Mitochondrial Phosphatase in the Regulation of ATP Production and Insulin Secretion in Pancreatic beta Cells

Pagliarini DJ, Wiley SE, Kimple ME, Dixon JR, Kelly P, Worby CA, Casey PJ and Dixon JE
Source: Mol Cell
Publication Date: (2005)
Issue: 19(2): 197-207
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
INS1 832/13
Species: rat
Tissue Origin: pancreas
Nucleofector® I/II/2b
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.