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Broad Remodeling of the Acetylproteo...

Peterson, Brett Steven.

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Broad Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β-cell Metabolism in the Absence of Dietary Overnutrition.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Broad Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β-cell Metabolism in the Absence of Dietary Overnutrition./
Author:	Peterson, Brett Steven.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
Description:	151 p.
Notes:	Source: Dissertations Abstracts International, Volume: 79-11, Section: B.
Contained By:	Dissertations Abstracts International79-11B.
Subject:	Cellular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10750887
ISBN:	9780355913866

Broad Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β-cell Metabolism in the Absence of Dietary Overnutrition.
Peterson, Brett Steven.

Broad Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β-cell Metabolism in the Absence of Dietary Overnutrition. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 151 p.

Source: Dissertations Abstracts International, Volume: 79-11, Section: B.

Thesis (Ph.D.)--Duke University, 2018.

This item is not available from ProQuest Dissertations & Theses.

SIRT3 is an NAD+-dependent mitochondrial protein deacetylase purported to influence cellular and systemic metabolism through modulation of the mitochondrial acetylproteome. Fuel-stimulated insulin secretion from pancreatic islets involves mitochondrial metabolism and might be susceptible to SIRT3-mediated effects. To investigate this idea, we used CRISPR/Cas9 technology to obtain complete SIRT3 knockout in the INS-1 832/13 insulinoma cell line. In the context of this SIRT3 knockout cell line, we "re-expressed" wild-type SIRT3, β-Galactosidase, or one of three catalytically inactive mutant forms of SIRT3 to generate lines representing a wide range of SIRT3 expression and mitochondrial protein deacetylase activity. We performed large-scale acetylproteome profiling by mass spectrometry on the different lines, and observed widespread, SIRT3-dependent changes in acetylation of enzymes involved in fatty acid oxidation, the TCA cycle, and the electron transport chain. Remarkably, despite these broad changes, the cell lines had indistinguishable insulin secretion responses to glucose or pyruvate, and exhibited no differences in function or viability in response to metabolic or ER stress-inducing agents. Moreover, metabolomic profiling revealed that, when compared to SIRT3-null cell lines, expression of wild-type SIRT3 does not result in appreciable changes in a host of organic acid, amino acid or fatty acid-derived acylcarnitine metabolites during glucose stimulation.

ISBN: 9780355913866Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

Mitochondria

Broad Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β-cell Metabolism in the Absence of Dietary Overnutrition.
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506 $a This item must not be sold to any third party vendors.
520 $a SIRT3 is an NAD+-dependent mitochondrial protein deacetylase purported to influence cellular and systemic metabolism through modulation of the mitochondrial acetylproteome. Fuel-stimulated insulin secretion from pancreatic islets involves mitochondrial metabolism and might be susceptible to SIRT3-mediated effects. To investigate this idea, we used CRISPR/Cas9 technology to obtain complete SIRT3 knockout in the INS-1 832/13 insulinoma cell line. In the context of this SIRT3 knockout cell line, we "re-expressed" wild-type SIRT3, β-Galactosidase, or one of three catalytically inactive mutant forms of SIRT3 to generate lines representing a wide range of SIRT3 expression and mitochondrial protein deacetylase activity. We performed large-scale acetylproteome profiling by mass spectrometry on the different lines, and observed widespread, SIRT3-dependent changes in acetylation of enzymes involved in fatty acid oxidation, the TCA cycle, and the electron transport chain. Remarkably, despite these broad changes, the cell lines had indistinguishable insulin secretion responses to glucose or pyruvate, and exhibited no differences in function or viability in response to metabolic or ER stress-inducing agents. Moreover, metabolomic profiling revealed that, when compared to SIRT3-null cell lines, expression of wild-type SIRT3 does not result in appreciable changes in a host of organic acid, amino acid or fatty acid-derived acylcarnitine metabolites during glucose stimulation.
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