Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic beta cells.
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.
Pagliarini
David J
DJ
Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Wiley
Sandra E
SE
Kimple
Michelle E
ME
Dixon
Jesse R
JR
Kelly
Patrick
P
Worby
Carolyn A
CA
Casey
Patrick J
PJ
Dixon
Jack E
JE
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
D007328:Insulin; D000255:Adenosine Triphosphate; D017027:Protein Tyrosine Phosphatases