TY - JOUR
T1 - Peroxisome proliferator-activated receptor γ co-activator 1 α (PGC-1α) and sirtuin 1 (SIRT1) reside in mitochondria
T2 - Possible direct function in mitochondrial biogenesis
AU - Aquilano, Katia
AU - Vigilanza, Paola
AU - Baldelli, Sara
AU - Pagliei, Beatrice
AU - Rotilio, Giuseppe
AU - Ciriolo, Maria Rosa
PY - 2010/7/9
Y1 - 2010/7/9
N2 - The transcriptional co-activator PGC-1αand the NAD +-dependent deacetylase SIRT1 are considered important inducers of mitochondrial biogenesis because in the nucleus they regulate transcription of nucleus-encoded mitochondrial genes. We demonstrate that PGC-1α and SIRT1 are also present inside mitochondria and are in close proximity to mtDNA. They interact with mitochondrial transcription factor A (TFAM) as assessed by confocal microscopy analysis and by blue native-PAGE. Nucleoid purification allowed us to identify SIRT1 and PGC-1α as proteins associated with native and cross-linked nucleoids, respectively. After mtDNA immunoprecipitation analysis, carried out on mitochondrial extracts, we found that PGC-1α is present on the same D-loop region recognized by TFAM. Finally, by oligonucleotide pulldown assay, we found PGC-1α and SIRT1 associated with the TFAM consensus sequence (human mitochondrial transcription factor-binding site H). The results obtained suggest that in mitochondria PGC-1αand SIRT1 may function as their nuclear counterparts and represent the genuine factors mediating the cross-talk between nuclear and mitochondrial genome. Finally, this work adds new knowledge on the function of SIRT1 and PGC-1αand highlights the direct involvement of such proteins in regulation of mitochondrial biogenesis.
AB - The transcriptional co-activator PGC-1αand the NAD +-dependent deacetylase SIRT1 are considered important inducers of mitochondrial biogenesis because in the nucleus they regulate transcription of nucleus-encoded mitochondrial genes. We demonstrate that PGC-1α and SIRT1 are also present inside mitochondria and are in close proximity to mtDNA. They interact with mitochondrial transcription factor A (TFAM) as assessed by confocal microscopy analysis and by blue native-PAGE. Nucleoid purification allowed us to identify SIRT1 and PGC-1α as proteins associated with native and cross-linked nucleoids, respectively. After mtDNA immunoprecipitation analysis, carried out on mitochondrial extracts, we found that PGC-1α is present on the same D-loop region recognized by TFAM. Finally, by oligonucleotide pulldown assay, we found PGC-1α and SIRT1 associated with the TFAM consensus sequence (human mitochondrial transcription factor-binding site H). The results obtained suggest that in mitochondria PGC-1αand SIRT1 may function as their nuclear counterparts and represent the genuine factors mediating the cross-talk between nuclear and mitochondrial genome. Finally, this work adds new knowledge on the function of SIRT1 and PGC-1αand highlights the direct involvement of such proteins in regulation of mitochondrial biogenesis.
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U2 - 10.1074/jbc.M109.070169
DO - 10.1074/jbc.M109.070169
M3 - Article
C2 - 20448046
AN - SCOPUS:77954353059
VL - 285
SP - 21590
EP - 21599
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 28
ER -