Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival

Junghee Lee, Chun Hyung Kim, David K. Simon, Lyaylya R. Aminova, Alexander Y. Andreyev, Yulia E. Kushnareva, Anne N. Murphy, Bonnie E. Lonze, Kwang Soo Kim, David D. Ginty, Robert J. Ferrante, Hoon Ryu, Rajiv R. Ratan

Research output: Contribution to journalArticle

Abstract

Cyclic AMP response element-binding protein (CREB) is a widely expressed transcription factor whose role in neuronal protection is now well established. Here we report that CREB is present in the mitochondrial matrix of neurons and that it binds directly to cyclic AMP response elements (CREs) found within the mitochondrial genome. Disruption of CREB activity in the mitochondria decreases the expression of a subset of mitochondrial genes, including the ND5 subunit of complex I, down-regulates complex I-dependent mitochondrial respiration, and increases susceptibility to 3-nitropropionic acid, a mitochondrial toxin that induces a clinical and pathological phenotype similar to Huntington disease. These results demonstrate that regulation of mitochondrial gene expression by mitochondrial CREB, in part, underlies the protective effects of CREB and raise the possibility that decreased mitochondrial CREB activity contributes to the mitochondrial dysfunction and neuronal loss associated with neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)40398-40401
Number of pages4
JournalJournal of Biological Chemistry
Volume280
Issue number49
DOIs
StatePublished - Dec 9 2005

Fingerprint

Cyclic AMP Response Element-Binding Protein
Mitochondrial Genes
Mitochondrial Proteins
Gene expression
Gene Expression
Genes
Mitochondria
Mitochondrial Genome
Huntington Disease
Gene Expression Regulation
Response Elements
Neurodegenerative Diseases
Cyclic AMP
Neurons
Respiration
Transcription Factors
Down-Regulation
Phenotype

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lee, J., Kim, C. H., Simon, D. K., Aminova, L. R., Andreyev, A. Y., Kushnareva, Y. E., ... Ratan, R. R. (2005). Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival. Journal of Biological Chemistry, 280(49), 40398-40401. https://doi.org/10.1074/jbc.C500140200

Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival. / Lee, Junghee; Kim, Chun Hyung; Simon, David K.; Aminova, Lyaylya R.; Andreyev, Alexander Y.; Kushnareva, Yulia E.; Murphy, Anne N.; Lonze, Bonnie E.; Kim, Kwang Soo; Ginty, David D.; Ferrante, Robert J.; Ryu, Hoon; Ratan, Rajiv R.

In: Journal of Biological Chemistry, Vol. 280, No. 49, 09.12.2005, p. 40398-40401.

Research output: Contribution to journalArticle

Lee, J, Kim, CH, Simon, DK, Aminova, LR, Andreyev, AY, Kushnareva, YE, Murphy, AN, Lonze, BE, Kim, KS, Ginty, DD, Ferrante, RJ, Ryu, H & Ratan, RR 2005, 'Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival', Journal of Biological Chemistry, vol. 280, no. 49, pp. 40398-40401. https://doi.org/10.1074/jbc.C500140200
Lee, Junghee ; Kim, Chun Hyung ; Simon, David K. ; Aminova, Lyaylya R. ; Andreyev, Alexander Y. ; Kushnareva, Yulia E. ; Murphy, Anne N. ; Lonze, Bonnie E. ; Kim, Kwang Soo ; Ginty, David D. ; Ferrante, Robert J. ; Ryu, Hoon ; Ratan, Rajiv R. / Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 49. pp. 40398-40401.
@article{c4a75c2942944c1c917f7f00530a6366,
title = "Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival",
abstract = "Cyclic AMP response element-binding protein (CREB) is a widely expressed transcription factor whose role in neuronal protection is now well established. Here we report that CREB is present in the mitochondrial matrix of neurons and that it binds directly to cyclic AMP response elements (CREs) found within the mitochondrial genome. Disruption of CREB activity in the mitochondria decreases the expression of a subset of mitochondrial genes, including the ND5 subunit of complex I, down-regulates complex I-dependent mitochondrial respiration, and increases susceptibility to 3-nitropropionic acid, a mitochondrial toxin that induces a clinical and pathological phenotype similar to Huntington disease. These results demonstrate that regulation of mitochondrial gene expression by mitochondrial CREB, in part, underlies the protective effects of CREB and raise the possibility that decreased mitochondrial CREB activity contributes to the mitochondrial dysfunction and neuronal loss associated with neurodegenerative disorders.",
author = "Junghee Lee and Kim, {Chun Hyung} and Simon, {David K.} and Aminova, {Lyaylya R.} and Andreyev, {Alexander Y.} and Kushnareva, {Yulia E.} and Murphy, {Anne N.} and Lonze, {Bonnie E.} and Kim, {Kwang Soo} and Ginty, {David D.} and Ferrante, {Robert J.} and Hoon Ryu and Ratan, {Rajiv R.}",
year = "2005",
month = "12",
day = "9",
doi = "10.1074/jbc.C500140200",
language = "English (US)",
volume = "280",
pages = "40398--40401",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "49",

}

TY - JOUR

T1 - Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival

AU - Lee, Junghee

AU - Kim, Chun Hyung

AU - Simon, David K.

AU - Aminova, Lyaylya R.

AU - Andreyev, Alexander Y.

AU - Kushnareva, Yulia E.

AU - Murphy, Anne N.

AU - Lonze, Bonnie E.

AU - Kim, Kwang Soo

AU - Ginty, David D.

AU - Ferrante, Robert J.

AU - Ryu, Hoon

AU - Ratan, Rajiv R.

PY - 2005/12/9

Y1 - 2005/12/9

N2 - Cyclic AMP response element-binding protein (CREB) is a widely expressed transcription factor whose role in neuronal protection is now well established. Here we report that CREB is present in the mitochondrial matrix of neurons and that it binds directly to cyclic AMP response elements (CREs) found within the mitochondrial genome. Disruption of CREB activity in the mitochondria decreases the expression of a subset of mitochondrial genes, including the ND5 subunit of complex I, down-regulates complex I-dependent mitochondrial respiration, and increases susceptibility to 3-nitropropionic acid, a mitochondrial toxin that induces a clinical and pathological phenotype similar to Huntington disease. These results demonstrate that regulation of mitochondrial gene expression by mitochondrial CREB, in part, underlies the protective effects of CREB and raise the possibility that decreased mitochondrial CREB activity contributes to the mitochondrial dysfunction and neuronal loss associated with neurodegenerative disorders.

AB - Cyclic AMP response element-binding protein (CREB) is a widely expressed transcription factor whose role in neuronal protection is now well established. Here we report that CREB is present in the mitochondrial matrix of neurons and that it binds directly to cyclic AMP response elements (CREs) found within the mitochondrial genome. Disruption of CREB activity in the mitochondria decreases the expression of a subset of mitochondrial genes, including the ND5 subunit of complex I, down-regulates complex I-dependent mitochondrial respiration, and increases susceptibility to 3-nitropropionic acid, a mitochondrial toxin that induces a clinical and pathological phenotype similar to Huntington disease. These results demonstrate that regulation of mitochondrial gene expression by mitochondrial CREB, in part, underlies the protective effects of CREB and raise the possibility that decreased mitochondrial CREB activity contributes to the mitochondrial dysfunction and neuronal loss associated with neurodegenerative disorders.

UR - http://www.scopus.com/inward/record.url?scp=28844499005&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28844499005&partnerID=8YFLogxK

U2 - 10.1074/jbc.C500140200

DO - 10.1074/jbc.C500140200

M3 - Article

C2 - 16207717

AN - SCOPUS:28844499005

VL - 280

SP - 40398

EP - 40401

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 49

ER -