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

• Published in: Molecular cell 2005-07, Vol.19 (2), p.197-207
• Main Authors: Pagliarini, David J., Wiley, Sandra E., Kimple, Michelle E., Dixon, Jesse R., Kelly, Patrick, Worby, Carolyn A., Casey, Patrick J., Dixon, Jack E.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - biosynthesis; Adenosine Triphosphate - metabolism; Amino Acid Sequence; Animals; Cercopithecus aethiops; Cloning, Molecular; COS Cells; 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
• ISSN: 1097-2765; 1097-4164
• 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 Mi tochondrion 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.