Amyloid precursor protein, heat-shock proteins, and Bcl-2 form a complex in mitochondria and modulate mitochondria function and apoptosis in N2a cells

Ting Ting Yang, Chao Tien Hsu, Yu-Min Kuo

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Neurons that degenerate in the brains of persons with Alzheimer's disease accumulate mitochondrial amyloid precursor protein (APP), which is thought to negatively affect mitochondrial function and cellular homeostasis. Because proteins that enter mitochondria require assistance from chaperone proteins, we hypothesized that heat-shock proteins (HSPs) help accumulate APP in mitochondria. We found that APP overexpression in N2a cells (APP cells) did not elicit mitochondrial dysfunction. Because cerebral hypoperfusion-associated energy deficiency is an important etiology for Alzheimer's disease, we also challenged the cells with serum starvation. APP/HSP/Bcl-2 complexes formed within the mitochondria of serum-starved APP cells, but not control cells. Mitochondria containing APP/HSP/Bcl-2 complexes induced apoptosis. We hypothesize that APP/HSP/Bcl-2 complexes diminish the functional capacities of HSPs and Bcl-2, which leads to mitochondrial injury and apoptosis.

Original languageEnglish
Pages (from-to)592-601
Number of pages10
JournalMechanisms of Ageing and Development
Volume130
Issue number9
DOIs
Publication statusPublished - 2009 Sep 1

Fingerprint

Amyloid beta-Protein Precursor
Heat-Shock Proteins
Mitochondria
Apoptosis
Alzheimer Disease
Mitochondrial Proteins
Starvation
Serum
Amyloid
Proteins
Homeostasis
Neurons
Wounds and Injuries
Brain

All Science Journal Classification (ASJC) codes

  • Ageing
  • Developmental Biology

Cite this

@article{875424dd45cf45a8b1b516802ec52f3d,
title = "Amyloid precursor protein, heat-shock proteins, and Bcl-2 form a complex in mitochondria and modulate mitochondria function and apoptosis in N2a cells",
abstract = "Neurons that degenerate in the brains of persons with Alzheimer's disease accumulate mitochondrial amyloid precursor protein (APP), which is thought to negatively affect mitochondrial function and cellular homeostasis. Because proteins that enter mitochondria require assistance from chaperone proteins, we hypothesized that heat-shock proteins (HSPs) help accumulate APP in mitochondria. We found that APP overexpression in N2a cells (APP cells) did not elicit mitochondrial dysfunction. Because cerebral hypoperfusion-associated energy deficiency is an important etiology for Alzheimer's disease, we also challenged the cells with serum starvation. APP/HSP/Bcl-2 complexes formed within the mitochondria of serum-starved APP cells, but not control cells. Mitochondria containing APP/HSP/Bcl-2 complexes induced apoptosis. We hypothesize that APP/HSP/Bcl-2 complexes diminish the functional capacities of HSPs and Bcl-2, which leads to mitochondrial injury and apoptosis.",
author = "Yang, {Ting Ting} and Hsu, {Chao Tien} and Yu-Min Kuo",
year = "2009",
month = "9",
day = "1",
doi = "10.1016/j.mad.2009.07.002",
language = "English",
volume = "130",
pages = "592--601",
journal = "Mechanisms of Ageing and Development",
issn = "0047-6374",
publisher = "Elsevier Ireland Ltd",
number = "9",

}

Amyloid precursor protein, heat-shock proteins, and Bcl-2 form a complex in mitochondria and modulate mitochondria function and apoptosis in N2a cells. / Yang, Ting Ting; Hsu, Chao Tien; Kuo, Yu-Min.

In: Mechanisms of Ageing and Development, Vol. 130, No. 9, 01.09.2009, p. 592-601.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Amyloid precursor protein, heat-shock proteins, and Bcl-2 form a complex in mitochondria and modulate mitochondria function and apoptosis in N2a cells

AU - Yang, Ting Ting

AU - Hsu, Chao Tien

AU - Kuo, Yu-Min

PY - 2009/9/1

Y1 - 2009/9/1

N2 - Neurons that degenerate in the brains of persons with Alzheimer's disease accumulate mitochondrial amyloid precursor protein (APP), which is thought to negatively affect mitochondrial function and cellular homeostasis. Because proteins that enter mitochondria require assistance from chaperone proteins, we hypothesized that heat-shock proteins (HSPs) help accumulate APP in mitochondria. We found that APP overexpression in N2a cells (APP cells) did not elicit mitochondrial dysfunction. Because cerebral hypoperfusion-associated energy deficiency is an important etiology for Alzheimer's disease, we also challenged the cells with serum starvation. APP/HSP/Bcl-2 complexes formed within the mitochondria of serum-starved APP cells, but not control cells. Mitochondria containing APP/HSP/Bcl-2 complexes induced apoptosis. We hypothesize that APP/HSP/Bcl-2 complexes diminish the functional capacities of HSPs and Bcl-2, which leads to mitochondrial injury and apoptosis.

AB - Neurons that degenerate in the brains of persons with Alzheimer's disease accumulate mitochondrial amyloid precursor protein (APP), which is thought to negatively affect mitochondrial function and cellular homeostasis. Because proteins that enter mitochondria require assistance from chaperone proteins, we hypothesized that heat-shock proteins (HSPs) help accumulate APP in mitochondria. We found that APP overexpression in N2a cells (APP cells) did not elicit mitochondrial dysfunction. Because cerebral hypoperfusion-associated energy deficiency is an important etiology for Alzheimer's disease, we also challenged the cells with serum starvation. APP/HSP/Bcl-2 complexes formed within the mitochondria of serum-starved APP cells, but not control cells. Mitochondria containing APP/HSP/Bcl-2 complexes induced apoptosis. We hypothesize that APP/HSP/Bcl-2 complexes diminish the functional capacities of HSPs and Bcl-2, which leads to mitochondrial injury and apoptosis.

UR - http://www.scopus.com/inward/record.url?scp=69949108391&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69949108391&partnerID=8YFLogxK

U2 - 10.1016/j.mad.2009.07.002

DO - 10.1016/j.mad.2009.07.002

M3 - Article

C2 - 19622370

AN - SCOPUS:69949108391

VL - 130

SP - 592

EP - 601

JO - Mechanisms of Ageing and Development

JF - Mechanisms of Ageing and Development

SN - 0047-6374

IS - 9

ER -