Journal
CURRENT MOLECULAR MEDICINE
Volume 13, Issue 1, Pages 140-154Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156652413804486241
Keywords
Biogenesis; cellular metabolism; cytoplasm; mitochondria; mitochondrial diseases; transcriptional regulation
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Funding
- MIUR
- Fondazione Roma
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SIRT1 and PGC-1 alpha are two nutrient sensing master regulators of cellular metabolism and their up-regulation is often linked to increased lifespan. SIRT1 and PGC-1 alpha 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-1 alpha. Then, data from papers demonstrating the presence of SIRT1 and PGC-1 alpha 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-1 alpha in human mitochondrial diseases will be described and the possible role of their mitochondrial forms will be briefly discussed.
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