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:Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 1, 00133 Rome, Italy.
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.
