Early dysregulation of the mitochondrial proteome in a mouse model of Alzheimer's disease

Jose L. Chou, Deepa V. Shenoy, Nicy Thomas, Pankaj K. Choudhary, Frank M. LaFerla, Steven Goodman, Gail A.M. Breen

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Mitochondrial structural and functional alterations appear to play to an important role in the pathogenesis of Alzheimer's disease (AD). In the present study, we used a quantitative comparative proteomic profiling approach to analyze changes in the mitochondrial proteome in AD. A triple transgenic mouse model of AD (3xTg-AD) which harbors mutations in three human transgenes, APP Swe , PS1 M146V and Tau P301L , was used in these experiments. Quantitative differences in the mitochondrial proteome between the cerebral cortices of 6-month-old male 3xTg-AD and non-transgenic mice were determined by using two-dimensional difference gel electrophoresis (2D-DIGE) and tandem mass spectrometry. We identified 23 different proteins whose expression levels differed significantly between triple transgenic and non-transgenic mitochondria. Both down-regulated and up-regulated mitochondrial proteins were observed in transgenic AD cortices. Proteins which were dysregulated in 3xTg-AD cortices functioned in a wide variety of metabolic pathways, including the citric acid cycle, oxidative phosphorylation, pyruvate metabolism, glycolysis, oxidative stress, fatty acid oxidation, ketone body metabolism, ion transport, apoptosis, and mitochondrial protein synthesis. These alterations in the mitochondrial proteome of the cerebral cortices of triple transgenic AD mice occurred before the development of significant amyloid plaque and neurofibrillary tangles, indicating that mitochondrial dysregulation is an early event in AD.

Original languageEnglish (US)
Pages (from-to)466-479
Number of pages14
JournalJournal of Proteomics
Volume74
Issue number4
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

Fingerprint

Proteome
Alzheimer Disease
Two-Dimensional Difference Gel Electrophoresis
Mitochondrial Proteins
Metabolism
Cerebral Cortex
Ketone Bodies
Neurofibrillary Tangles
Mitochondria
Oxidative stress
Citric Acid Cycle
Oxidative Phosphorylation
Ion Transport
Amyloid Plaques
Glycolysis
Ports and harbors
Tandem Mass Spectrometry
Metabolic Networks and Pathways
Electrophoresis
Pyruvic Acid

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry

Cite this

Chou, J. L., Shenoy, D. V., Thomas, N., Choudhary, P. K., LaFerla, F. M., Goodman, S., & Breen, G. A. M. (2011). Early dysregulation of the mitochondrial proteome in a mouse model of Alzheimer's disease. Journal of Proteomics, 74(4), 466-479. https://doi.org/10.1016/j.jprot.2010.12.012

Early dysregulation of the mitochondrial proteome in a mouse model of Alzheimer's disease. / Chou, Jose L.; Shenoy, Deepa V.; Thomas, Nicy; Choudhary, Pankaj K.; LaFerla, Frank M.; Goodman, Steven; Breen, Gail A.M.

In: Journal of Proteomics, Vol. 74, No. 4, 01.04.2011, p. 466-479.

Research output: Contribution to journalArticle

Chou, JL, Shenoy, DV, Thomas, N, Choudhary, PK, LaFerla, FM, Goodman, S & Breen, GAM 2011, 'Early dysregulation of the mitochondrial proteome in a mouse model of Alzheimer's disease', Journal of Proteomics, vol. 74, no. 4, pp. 466-479. https://doi.org/10.1016/j.jprot.2010.12.012
Chou, Jose L. ; Shenoy, Deepa V. ; Thomas, Nicy ; Choudhary, Pankaj K. ; LaFerla, Frank M. ; Goodman, Steven ; Breen, Gail A.M. / Early dysregulation of the mitochondrial proteome in a mouse model of Alzheimer's disease. In: Journal of Proteomics. 2011 ; Vol. 74, No. 4. pp. 466-479.
@article{5870c6a320f44d74891550e48820a373,
title = "Early dysregulation of the mitochondrial proteome in a mouse model of Alzheimer's disease",
abstract = "Mitochondrial structural and functional alterations appear to play to an important role in the pathogenesis of Alzheimer's disease (AD). In the present study, we used a quantitative comparative proteomic profiling approach to analyze changes in the mitochondrial proteome in AD. A triple transgenic mouse model of AD (3xTg-AD) which harbors mutations in three human transgenes, APP Swe , PS1 M146V and Tau P301L , was used in these experiments. Quantitative differences in the mitochondrial proteome between the cerebral cortices of 6-month-old male 3xTg-AD and non-transgenic mice were determined by using two-dimensional difference gel electrophoresis (2D-DIGE) and tandem mass spectrometry. We identified 23 different proteins whose expression levels differed significantly between triple transgenic and non-transgenic mitochondria. Both down-regulated and up-regulated mitochondrial proteins were observed in transgenic AD cortices. Proteins which were dysregulated in 3xTg-AD cortices functioned in a wide variety of metabolic pathways, including the citric acid cycle, oxidative phosphorylation, pyruvate metabolism, glycolysis, oxidative stress, fatty acid oxidation, ketone body metabolism, ion transport, apoptosis, and mitochondrial protein synthesis. These alterations in the mitochondrial proteome of the cerebral cortices of triple transgenic AD mice occurred before the development of significant amyloid plaque and neurofibrillary tangles, indicating that mitochondrial dysregulation is an early event in AD.",
author = "Chou, {Jose L.} and Shenoy, {Deepa V.} and Nicy Thomas and Choudhary, {Pankaj K.} and LaFerla, {Frank M.} and Steven Goodman and Breen, {Gail A.M.}",
year = "2011",
month = "4",
day = "1",
doi = "10.1016/j.jprot.2010.12.012",
language = "English (US)",
volume = "74",
pages = "466--479",
journal = "Journal of Proteomics",
issn = "1874-3919",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - Early dysregulation of the mitochondrial proteome in a mouse model of Alzheimer's disease

AU - Chou, Jose L.

AU - Shenoy, Deepa V.

AU - Thomas, Nicy

AU - Choudhary, Pankaj K.

AU - LaFerla, Frank M.

AU - Goodman, Steven

AU - Breen, Gail A.M.

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Mitochondrial structural and functional alterations appear to play to an important role in the pathogenesis of Alzheimer's disease (AD). In the present study, we used a quantitative comparative proteomic profiling approach to analyze changes in the mitochondrial proteome in AD. A triple transgenic mouse model of AD (3xTg-AD) which harbors mutations in three human transgenes, APP Swe , PS1 M146V and Tau P301L , was used in these experiments. Quantitative differences in the mitochondrial proteome between the cerebral cortices of 6-month-old male 3xTg-AD and non-transgenic mice were determined by using two-dimensional difference gel electrophoresis (2D-DIGE) and tandem mass spectrometry. We identified 23 different proteins whose expression levels differed significantly between triple transgenic and non-transgenic mitochondria. Both down-regulated and up-regulated mitochondrial proteins were observed in transgenic AD cortices. Proteins which were dysregulated in 3xTg-AD cortices functioned in a wide variety of metabolic pathways, including the citric acid cycle, oxidative phosphorylation, pyruvate metabolism, glycolysis, oxidative stress, fatty acid oxidation, ketone body metabolism, ion transport, apoptosis, and mitochondrial protein synthesis. These alterations in the mitochondrial proteome of the cerebral cortices of triple transgenic AD mice occurred before the development of significant amyloid plaque and neurofibrillary tangles, indicating that mitochondrial dysregulation is an early event in AD.

AB - Mitochondrial structural and functional alterations appear to play to an important role in the pathogenesis of Alzheimer's disease (AD). In the present study, we used a quantitative comparative proteomic profiling approach to analyze changes in the mitochondrial proteome in AD. A triple transgenic mouse model of AD (3xTg-AD) which harbors mutations in three human transgenes, APP Swe , PS1 M146V and Tau P301L , was used in these experiments. Quantitative differences in the mitochondrial proteome between the cerebral cortices of 6-month-old male 3xTg-AD and non-transgenic mice were determined by using two-dimensional difference gel electrophoresis (2D-DIGE) and tandem mass spectrometry. We identified 23 different proteins whose expression levels differed significantly between triple transgenic and non-transgenic mitochondria. Both down-regulated and up-regulated mitochondrial proteins were observed in transgenic AD cortices. Proteins which were dysregulated in 3xTg-AD cortices functioned in a wide variety of metabolic pathways, including the citric acid cycle, oxidative phosphorylation, pyruvate metabolism, glycolysis, oxidative stress, fatty acid oxidation, ketone body metabolism, ion transport, apoptosis, and mitochondrial protein synthesis. These alterations in the mitochondrial proteome of the cerebral cortices of triple transgenic AD mice occurred before the development of significant amyloid plaque and neurofibrillary tangles, indicating that mitochondrial dysregulation is an early event in AD.

UR - http://www.scopus.com/inward/record.url?scp=79952247298&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952247298&partnerID=8YFLogxK

U2 - 10.1016/j.jprot.2010.12.012

DO - 10.1016/j.jprot.2010.12.012

M3 - Article

VL - 74

SP - 466

EP - 479

JO - Journal of Proteomics

JF - Journal of Proteomics

SN - 1874-3919

IS - 4

ER -