Abstract
SIRT1 and PGC-1α are two nutrient sensing master regulators of cellular metabolism and their upregulation is often linked to increased lifespan. SIRT1 and PGC-1α modulate the expression of a set of nuclear genes controlling many metabolic pathways. In recent years mounting evidence has indicated the implication of these proteins in several mitochondrial diseases including neurodegenerative disorders, myopathies and Type II diabetes mellitus. Recently, these proteins have been localized in cytoplasm and mitochondria wherein they target novel substrates opening new insight into their possible function in modulating extranuclear genes and proteins. This review will firstly summarize the nuclear function of SIRT1 and PGC-1α. Then, data from papers demonstrating the presence of SIRT1 and PGC-1α in the cytoplasm and in mitochondria will be outlined so that these extranuclear forms do not remain out of sight. Finally, very recent evidence of the alteration of the pathways governed by SIRT1 and PGC-1α in human mitochondrial diseases will be described and the possible role of their mitochondrial forms will be briefly discussed.
Keywords: Biogenesis, cellular metabolism, cytoplasm, mitochondria, mitochondrial diseases, transcriptional regulation
Current Molecular Medicine
Title:Extranuclear Localization of SIRT1 and PGC-1α: An Insight into Possible Roles in Diseases Associated with Mitochondrial Dysfunction
Volume: 13 Issue: 1
Author(s): K. Aquilano, S. Baldelli, B. Pagliei and M. R. Ciriolo
Affiliation:
Keywords: Biogenesis, cellular metabolism, cytoplasm, mitochondria, mitochondrial diseases, transcriptional regulation
Abstract: SIRT1 and PGC-1α are two nutrient sensing master regulators of cellular metabolism and their upregulation is often linked to increased lifespan. SIRT1 and PGC-1α modulate the expression of a set of nuclear genes controlling many metabolic pathways. In recent years mounting evidence has indicated the implication of these proteins in several mitochondrial diseases including neurodegenerative disorders, myopathies and Type II diabetes mellitus. Recently, these proteins have been localized in cytoplasm and mitochondria wherein they target novel substrates opening new insight into their possible function in modulating extranuclear genes and proteins. This review will firstly summarize the nuclear function of SIRT1 and PGC-1α. Then, data from papers demonstrating the presence of SIRT1 and PGC-1α in the cytoplasm and in mitochondria will be outlined so that these extranuclear forms do not remain out of sight. Finally, very recent evidence of the alteration of the pathways governed by SIRT1 and PGC-1α in human mitochondrial diseases will be described and the possible role of their mitochondrial forms will be briefly discussed.
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Cite this article as:
Aquilano K., Baldelli S., Pagliei B. and R. Ciriolo M., Extranuclear Localization of SIRT1 and PGC-1α: An Insight into Possible Roles in Diseases Associated with Mitochondrial Dysfunction, Current Molecular Medicine 2013; 13 (1) . https://dx.doi.org/10.2174/1566524011307010140
DOI https://dx.doi.org/10.2174/1566524011307010140 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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