Publication

Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration

Siudeja, K., Srinivasan, B., Xu, L., Rana, A., de Jong, J., Nollen, E. A. A., Jackowski, S., Sanford, L., Hayflick, S. & Sibon, O. C. M., Dec-2011, In : EMBO Molecular Medicine. 3, 12, p. 755-766 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Siudeja, K., Srinivasan, B., Xu, L., Rana, A., de Jong, J., Nollen, E. A. A., ... Sibon, O. C. M. (2011). Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration. EMBO Molecular Medicine, 3(12), 755-766. https://doi.org/10.1002/emmm.201100180

Author

Siudeja, Katarzyna ; Srinivasan, Balaji ; Xu, Lanjun ; Rana, Anil ; de Jong, Jannie ; Nollen, Ellen A. A. ; Jackowski, Suzanne ; Sanford, Lynn ; Hayflick, Susan ; Sibon, Ody C. M. / Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration. In: EMBO Molecular Medicine. 2011 ; Vol. 3, No. 12. pp. 755-766.

Harvard

Siudeja, K, Srinivasan, B, Xu, L, Rana, A, de Jong, J, Nollen, EAA, Jackowski, S, Sanford, L, Hayflick, S & Sibon, OCM 2011, 'Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration', EMBO Molecular Medicine, vol. 3, no. 12, pp. 755-766. https://doi.org/10.1002/emmm.201100180

Standard

Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration. / Siudeja, Katarzyna; Srinivasan, Balaji; Xu, Lanjun; Rana, Anil; de Jong, Jannie; Nollen, Ellen A. A.; Jackowski, Suzanne; Sanford, Lynn; Hayflick, Susan; Sibon, Ody C. M.

In: EMBO Molecular Medicine, Vol. 3, No. 12, 12.2011, p. 755-766.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Siudeja K, Srinivasan B, Xu L, Rana A, de Jong J, Nollen EAA et al. Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration. EMBO Molecular Medicine. 2011 Dec;3(12):755-766. https://doi.org/10.1002/emmm.201100180


BibTeX

@article{58000b71105d432c89a266a42a66de7e,
title = "Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration",
abstract = "Pantothenate kinase-associated neurodegeneration (PKAN is a neurodegenerative disease with unresolved pathophysiology. Previously, we observed reduced Coenzyme A levels in a Drosophila model for PKAN. Coenzyme A is required for acetyl-Coenzyme A synthesis and acyl groups from the latter are transferred to lysine residues of proteins, in a reaction regulated by acetyltransferases. The tight balance between acetyltransferases and their antagonistic counterparts histone deacetylases is a well-known determining factor for the acetylation status of proteins. However, the influence of Coenzyme A levels on protein acetylation is unknown. Here we investigate whether decreased levels of the central metabolite Coenzyme A induce alterations in protein acetylation and whether this correlates with specific phenotypes of PKAN models. We show that in various organisms proper Coenzyme A metabolism is required for maintenance of histone- and tubulin acetylation, and decreased acetylation of these proteins is associated with an impaired DNA damage response, decreased locomotor function and decreased survival. Decreased protein acetylation and the concurrent phenotypes are partly rescued by pantethine and HDAC inhibitors, suggesting possible directions for future PKAN therapy development.",
keywords = "DNA damage, HDAC inhibitors, NBIA, PKAN, protein acetylation, ALPHA-TUBULIN, LYSINE 56, ACETYLTRANSFERASE, TRANSCRIPTION, DEACETYLATION, SYNTHETASE, COMPLEXES, MAMMALS, REPAIR, BREAKS",
author = "Katarzyna Siudeja and Balaji Srinivasan and Lanjun Xu and Anil Rana and {de Jong}, Jannie and Nollen, {Ellen A. A.} and Suzanne Jackowski and Lynn Sanford and Susan Hayflick and Sibon, {Ody C. M.}",
year = "2011",
month = "12",
doi = "10.1002/emmm.201100180",
language = "English",
volume = "3",
pages = "755--766",
journal = "EMBO Molecular Medicine",
issn = "1757-4676",
publisher = "Wiley",
number = "12",

}

RIS

TY - JOUR

T1 - Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration

AU - Siudeja, Katarzyna

AU - Srinivasan, Balaji

AU - Xu, Lanjun

AU - Rana, Anil

AU - de Jong, Jannie

AU - Nollen, Ellen A. A.

AU - Jackowski, Suzanne

AU - Sanford, Lynn

AU - Hayflick, Susan

AU - Sibon, Ody C. M.

PY - 2011/12

Y1 - 2011/12

N2 - Pantothenate kinase-associated neurodegeneration (PKAN is a neurodegenerative disease with unresolved pathophysiology. Previously, we observed reduced Coenzyme A levels in a Drosophila model for PKAN. Coenzyme A is required for acetyl-Coenzyme A synthesis and acyl groups from the latter are transferred to lysine residues of proteins, in a reaction regulated by acetyltransferases. The tight balance between acetyltransferases and their antagonistic counterparts histone deacetylases is a well-known determining factor for the acetylation status of proteins. However, the influence of Coenzyme A levels on protein acetylation is unknown. Here we investigate whether decreased levels of the central metabolite Coenzyme A induce alterations in protein acetylation and whether this correlates with specific phenotypes of PKAN models. We show that in various organisms proper Coenzyme A metabolism is required for maintenance of histone- and tubulin acetylation, and decreased acetylation of these proteins is associated with an impaired DNA damage response, decreased locomotor function and decreased survival. Decreased protein acetylation and the concurrent phenotypes are partly rescued by pantethine and HDAC inhibitors, suggesting possible directions for future PKAN therapy development.

AB - Pantothenate kinase-associated neurodegeneration (PKAN is a neurodegenerative disease with unresolved pathophysiology. Previously, we observed reduced Coenzyme A levels in a Drosophila model for PKAN. Coenzyme A is required for acetyl-Coenzyme A synthesis and acyl groups from the latter are transferred to lysine residues of proteins, in a reaction regulated by acetyltransferases. The tight balance between acetyltransferases and their antagonistic counterparts histone deacetylases is a well-known determining factor for the acetylation status of proteins. However, the influence of Coenzyme A levels on protein acetylation is unknown. Here we investigate whether decreased levels of the central metabolite Coenzyme A induce alterations in protein acetylation and whether this correlates with specific phenotypes of PKAN models. We show that in various organisms proper Coenzyme A metabolism is required for maintenance of histone- and tubulin acetylation, and decreased acetylation of these proteins is associated with an impaired DNA damage response, decreased locomotor function and decreased survival. Decreased protein acetylation and the concurrent phenotypes are partly rescued by pantethine and HDAC inhibitors, suggesting possible directions for future PKAN therapy development.

KW - DNA damage

KW - HDAC inhibitors

KW - NBIA

KW - PKAN

KW - protein acetylation

KW - ALPHA-TUBULIN

KW - LYSINE 56

KW - ACETYLTRANSFERASE

KW - TRANSCRIPTION

KW - DEACETYLATION

KW - SYNTHETASE

KW - COMPLEXES

KW - MAMMALS

KW - REPAIR

KW - BREAKS

U2 - 10.1002/emmm.201100180

DO - 10.1002/emmm.201100180

M3 - Article

VL - 3

SP - 755

EP - 766

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

SN - 1757-4676

IS - 12

ER -

ID: 5455528