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

doi:10.1016/j.molcel.2005.06.008

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 journal › Article › peer-review

25 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 language	English
Pages (from-to)	197-207
Number of pages	11
Journal	Molecular cell
Volume	19
Issue number	2
DOIs	https://doi.org/10.1016/j.molcel.2005.06.008
State	Published - Jul 22 2005

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title = "Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic β 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.",

author = "Pagliarini, {David J.} and Wiley, {Sandra E.} and Kimple, {Michelle E.} and Dixon, {Jesse R.} and Patrick Kelly and Worby, {Carolyn A.} and Casey, {Patrick J.} and Dixon, {Jack E.}",

note = "Funding Information: We would like to thank Dr. Marilyn Farquhar and Timo Meerloo for their assistance in our immunogold EM experiments, Dr. Nissi Varki for her assistance with our IHC experiments, Dr. Anne Murphy for helpful discussions, and members of the Dixon lab for critical reading of the manuscript. This work was supported by National Institutes of Health Grant 18024 and funds from the Walther Cancer Institute (J.E.D.) and by National Institues of Health Pharmacology Training Grant NIH 2 T32 GM07752-25 (D.J.P.).",

year = "2005",

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doi = "10.1016/j.molcel.2005.06.008",

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AU - Wiley, Sandra E.

AU - Kimple, Michelle E.

AU - Dixon, Jesse R.

AU - Kelly, Patrick

AU - Worby, Carolyn A.

AU - Casey, Patrick J.

AU - Dixon, Jack E.

N1 - Funding Information: We would like to thank Dr. Marilyn Farquhar and Timo Meerloo for their assistance in our immunogold EM experiments, Dr. Nissi Varki for her assistance with our IHC experiments, Dr. Anne Murphy for helpful discussions, and members of the Dixon lab for critical reading of the manuscript. This work was supported by National Institutes of Health Grant 18024 and funds from the Walther Cancer Institute (J.E.D.) and by National Institues of Health Pharmacology Training Grant NIH 2 T32 GM07752-25 (D.J.P.).

PY - 2005/7/22

Y1 - 2005/7/22

N2 - 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.

AB - 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.

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JO - Molecular Cell

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

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