title: Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic beta cells.
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.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Pagliarini
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Wiley
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Kimple
authors.forename: Jesse R
authors.initials: JR
authors.lastname: Dixon
authors.forename: Patrick
authors.initials: P
authors.lastname: Kelly
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Worby
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Casey
authors.forename: Jack E
authors.initials: JE
authors.lastname: Dixon
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D008969:Molecular Sequence Data; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D013997:Time Factors
chemical_list: D007328:Insulin; D000255:Adenosine Triphosphate; D017027:Protein Tyrosine Phosphatases