Supplemental Table 1. Survival rates of PGC-1-/- mice (at weaning).
Genotype / Expected / Observed+/+ / 92 (25%) / 98 (27%)
+/- / 183 (50%)((50%) / 205 (56%)
-/- / 92 (25%) / 63 (17%) / P <0.01
Results are expressed as the total number of animals found with either genotype and the percentage of the total. Percentage (rounded) is given in parentheses.
Supplemental Table 2. Pathways upregulated by PGC-1 and PGC-1
PGC-1 / PGC-1Gene Ontology (GO)Pathway Name / Percent Changed (%) / Z Score / Percent Changed (%) / Z Score
organellar ribosome / 75.0 / 5.691 / 75.0 / 5.827
organellar large ribosomal subunit / 62.5 / 3.122 / 75.0 / 4.118
acyl-CoA dehydrogenase activity / 63.6 / 3.758 / 63.6 / 3.858
mitochondrial intermembrane space / 62.5 / 3.122 / 87.5 / 5.029
mitochondrial matrix / 54.3 / 5.304 / 54.3 / 5.466
mitochondrial ribosome / 75.0 / 5.691 / 75.0 / 5.827
mitochondrial large ribosomal subunit / 62.5 / 3.122 / 75.0 / 4.118
acetyl-CoA metabolic process / 57.9 / 4.304 / 52.6 / 3.837
tricarboxylic acid cycle / 64.7 / 4.786 / 58.8 / 4.287
chromatin silencing / 55.6 / 2.782 / 55.6 / 2.865
protein targeting to mitochondrion / 62.5 / 3.122 / 87.5 / 5.029
ubiquinone metabolic process / 71.4 / 3.521 / 85.7 / 4.582
ubiquinone biosynthetic process / 71.4 / 3.521 / 85.7 / 4.582
mitochondrial membrane organization and biogenesis / 58.3 / 3.457 / 58.3 / 3.557
aerobic respiration / 66.7 / 5.137 / 55.6 / 4.054
coenzyme catabolic process / 61.1 / 4.536 / 55.6 / 4.054
oxidoreductase activity, (acting on NADH or NADPH, quinone or similar compound as acceptor) / 56.3 / 3.781 / 50.0 / 3.249
heterochromatin formation / 55.6 / 2.782 / 55.6 / 2.865
mitochondrial lumen / 54.3 / 5.304 / 54.3 / 5.466
quinone cofactor metabolic process / 62.5 / 3.122 / 87.5 / 5.029
mitochondrial membrane part / 62.5 / 5.414 / 58.3 / 5.034
cellular respiration / 65.0 / 5.225 / 50.0 / 3.633
quinone cofactor biosynthetic process / 71.4 / 3.521 / 85.7 / 4.582
negative regulation of gene expression, epigenetic / 50.0 / 2.485 / 60.0 / 3.382
acetyl-CoA catabolic process / 64.7 / 4.786 / 58.8 / 4.287
cofactor catabolic process / 54.5 / 4.232 / 50.0 / 3.811
Clusteringand ranking were performed by usingGenMAPP software. Percentage changed was calculated as the number of genes changed (fold changes ≥ 1.5), divided by the number of genes measured in a pathway (Gene Ontology) * 100.
Supplemental Table 3. Mitochondrial genes upregulated by PGC-1 and PGC-1
PGC-1 / PGC-1Gene Name / Accession Number / Fold Changes / p / Fold Changes / p
Fatty Acid Oxidation
acetyl-coenzyme A acetyltransferase 1 / D13921 / 1.8 / 0.0089 / 1.8 / 0.0022
acetyl-Coenzyme A acyltransferase 2 / NM_130433 / 2.3 / 0.0030 / 2.2 / 0.0168
acetyl-coenzyme A dehydrogenase, medium chain / NM_016986 / 3.2 / 0.0121 / 2.5 / 0.0173
acyl-Coenzyme A dehydrogenase family, member 9 / BM391807 / 2.5 / 0.0358 / 3.9 / 0.0174
acyl-Coenzyme A dehydrogenase, very long chain / NM_012891 / 5.6 / 0.0010 / 3.9 / 0.0006
carnitine acetyltransferase / AI411979 / 1.9 / 0.0387 / 2.3 / 0.0069
carnitine palmitoyltransferase 1b / NM_013200 / 2.1 / 0.0286 / 2.1 / 0.0253
enoyl Coenzyme A hydratase, short chain, 1, mitochondrial / NM_078623 / 2.0 / 0.0085 / 2.1 / 0.0112
hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/ enoyl-Coenzyme A hydratase / AA800240 / 1.8 / 0.0225 / 1.8 / 0.0041
isocitrate dehydrogenase 3 (NAD+) alpha / NM_053638 / 4.6 / 0.0044 / 3.9 / 0.0152
isocitrate dehydrogenase 3 (NAD+) beta / AI171793 / 2.8 / 0.0029 / 2.4 / 0.0483
TCA Cycle
citrate synthase / NM_130755 / 2.7 / 0.0053 / 2.0 / 0.0257
fumarate hydratase 1 / NM_017005 / 2.0 / 0.0013 / 2.2 / 0.0093
succinate-CoA ligase, GDP-forming, alpha subunit / NM_053752 / 1.8 / 0.0054 / 1.7 / 0.0092
OXPHS
cytochrome c, somatic / AI104240 / 2.6 / 0.0368 / 2.0 / 0.0390
electron-transferring-flavoprotein dehydrogenase / AA851258 / 2.5 / 0.0121 / 3.2 / 0.0335
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 6 (B14) / AA819547 / 1.8 / 0.0235 / 1.9 / 0.0158
NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6, 17kDa / AI104528 / 2.1 / 0.0200 / 2.0 / 0.0025
NADH dehydrogenase (ubiquinone) 1, alpha/beta subcomplex, 1 / AA944343 / 1.8 / 0.0018 / 1.6 / 0.0210
succinate dehydrogenase complex, subunit D, integral membrane protein / AI410703 / 2.3 / 0.0016 / 1.8 / 0.0034
Glucose Oxidation
hexokinase 1 / NM_012734 / 1.6 / 0.0223 / 1.8 / 0.0154
malic enzyme 3, NADP(+)-dependent, mitochondrial / AI410864 / 2.6 / 0.0244 / 1.5 / 0.0358
Others
afadin / D90401 / 2.6 / 0.0124 / 2.2 / 0.0006
aldehyde dehydrogenase family 5, subfamily A1 / L34821 / 6.0 / 0.0207 / 3.9 / 0.0441
aminolevulinic acid synthase 1 / NM_024484 / 3.3 / 0.0022 / 2.5 / 0.0011
AU RNA binding protein/enoyl-coenzyme A hydratase / BM389502 / 1.8 / 0.0092 / 1.9 / 0.0414
branched chain keto acid dehydrogenase E1, beta polypeptide / BM385109 / 3.8 / 0.0090 / 4.0 / 0.0028
creatine kinase, brain / M14400 / 12.5 / 0.0026 / 7.7 / 0.0035
creatine kinase, mitochondrial 1, ubiquitous / BI301453 / 10.6 / 0.0006 / 9.8 / 0.0018
cysteine conjugate-beta lyase / BF400674 / 1.7 / 0.0367 / 2.4 / 0.0205
diazepam binding inhibitor / AI175009 / 1.9 / 0.0026 / 1.9 / 0.0035
endonuclease G / AA926357 / 5.3 / 0.0000 / 2.9 / 0.0001
ferredoxin 1 / NM_017126 / 3.6 / 0.0085 / 1.8 / 0.0187
ferredoxin reductase / NM_024153 / 2.2 / 0.0358 / 1.8 / 0.0202
heat shock protein, A / BI282281 / 2.3 / 0.0065 / 1.8 / 0.0455
HesB protein / BM384289 / 2.1 / 0.0070 / 1.7 / 0.0381
homolog of zebrafish ES1 / AI232270 / 1.8 / 0.0125 / 2.2 / 0.0048
inner membrane protein, mitochondrial / BI287936 / 2.2 / 0.0029 / 2.5 / 0.0029
lactamase, beta 2 / AI008160 / 2.2 / 0.0143 / 2.5 / 0.0076
leucine zipper-EF-hand containing transmembrane protein 1 / AI104605 / 2.1 / 0.0153 / 2.5 / 0.0496
leucine-rich PPR-motif containing / BI294727 / 3.0 / 0.0090 / 3.9 / 0.0180
matrix metalloproteinase 1a (interstitial collagenase) / BM386246 / 2.0 / 0.0139 / 1.6 / 0.0087
methylmalonyl CoA epimerase / BG379780 / 6.3 / 0.0008 / 5.1 / 0.0189
mitochondrial intermediate peptidase / NM_031052 / 1.6 / 0.0044 / 1.8 / 0.0157
mitochondrial ribosomal protein L1 / BI293704 / 2.4 / 0.0426 / 2.4 / 0.0289
mitochondrial ribosomal protein L14 / BE113348 / 3.0 / 0.0226 / 2.9 / 0.0123
mitochondrial ribosomal protein L18 / BI288800 / 2.4 / 0.0135 / 2.3 / 0.0144
mitochondrial ribosomal protein L2 / AI171870 / 2.2 / 0.0187 / 3.0 / 0.0043
mitochondrial ribosomal protein L3 / BI279024 / 2.0 / 0.0148 / 1.8 / 0.0319
mitochondrial ribosomal protein L35 / BF408394 / 2.4 / 0.0170 / 2.2 / 0.0036
mitochondrial ribosomal protein L38 / BG378538 / 5.0 / 0.0160 / 4.2 / 0.0199
mitochondrial ribosomal protein L46 / BI283167 / 2.4 / 0.0027 / 3.1 / 0.0099
mitochondrial ribosomal protein S17 / BM384239 / 1.7 / 0.0018 / 1.8 / 0.0361
mitochondrial ribosomal protein S18A / AA858667 / 2.1 / 0.0219 / 2.1 / 0.0025
mitochondrial ribosomal protein S23 / AI411153 / 2.1 / 0.0129 / 1.9 / 0.0259
mitochondrial ribosomal protein S33 / AI104277 / 3.0 / 0.0039 / 2.8 / 0.0006
mitochondrial ribosomal protein S34 / BI275958 / 1.7 / 0.0266 / 2.2 / 0.0405
mitochondrial ribosomal protein S36 / AW142276 / 3.0 / 0.0006 / 2.2 / 0.0026
mitochondrial ribosomal protein S5 / BM386940 / 2.1 / 0.0379 / 2.3 / 0.0296
mitochondrial ribosomal protein S9 / AI009481 / 1.7 / 0.0170 / 1.8 / 0.0231
mitofusin 2 / U41803 / 1.6 / 0.0113 / 2.0 / 0.0106
nitrogen fixation gene 1 (S. cerevisiae) / AI410876 / 4.5 / 0.0014 / 3.6 / 0.0073
nuclear receptor binding factor 1 / NM_017209 / 2.6 / 0.0396 / 2.5 / 0.0307
peptidase (mitochondrial processing) beta / NM_022395 / 1.6 / 0.0005 / 1.9 / 0.0072
peptidylprolyl isomerase F (cyclophilin F) / U68544 / 3.7 / 0.0066 / 3.0 / 0.0143
peroxiredoxin 3 / NM_022540 / 1.7 / 0.0021 / 1.9 / 0.0028
peroxiredoxin 5 / NM_053610 / 2.0 / 0.0074 / 2.0 / 0.0482
polymerase (DNA-directed), delta interacting protein 2 / AA851255 / 1.9 / 0.0095 / 2.3 / 0.0038
programmed cell death 8 / AF262320 / 1.8 / 0.0029 / 2.0 / 0.0088
protease, serine, 15 / NM_133404 / 2.1 / 0.0238 / 1.8 / 0.0415
ribosomal protein, mitochondrial, L2 / AA848353 / 2.2 / 0.0369 / 2.1 / 0.0194
solute carrier family 25 (carnitine/acylcarnitine translocase), member 20 / NM_053965 / 4.7 / 0.0008 / 3.8 / 0.0061
stomatin (Epb7.2)-like 2 / AA799462 / 1.6 / 0.0279 / 1.6 / 0.0265
thioesterase superfamily member 2 / AI411426 / 4.5 / 0.0077 / 2.9 / 0.0103
translocase of inner mitochondrial membrane 10 homolog (yeast) / AF150091 / 2.0 / 0.0083 / 1.6 / 0.0254
translocase of inner mitochondrial membrane 8 homolog a (yeast) / NM_053370 / 2.6 / 0.0056 / 1.9 / 0.0151
translocase of inner mitochondrial membrane 8 homolog b (yeast) / NM_022541 / 2.4 / 0.0081 / 2.5 / 0.0114
translocase of inner mitochondrial membrane 9 homolog (yeast) / BF282660 / 3.0 / 0.0479 / 2.3 / 0.0140
Tu translation elongation factor, mitochondrial / AI412102 / 2.0 / 0.0003 / 2.6 / 0.0245
v-raf murine sarcoma 3611 viral oncogene homolog 1 / NM_022532 / 2.2 / 0.0266 / 2.6 / 0.0003
P value was determined using Spotfire software. p< 0.05 compared to Ad-GFP control. Shown are the genes with a fold change≥ 1.5.
Supplemental Table 4. Survival rates of cardiac-specific PGC-1-/- mice (at weaning).
Genotype / Expected / Observed-/-f/+ / 9 (25%) / 11 (31%)
-/-f/f / 9 (25%) / 12 (34%)
-/-f/+/MHC-Cre / 9 (25%)
7 / 12 (34%)
-/-f/f/MHC-Cre / 9 (25%) / 0 (0%) / P < 0.01
Results for each genotype are expressed as a percentage of the total number of animals found at weaning (35). Percentage (rounded) is given in parentheses.
Supplemental Table 5. Sequences of mouse primers/probes used in real-time qPCR.
PGC-1 Exon 4-5(Ppargc1b) / FWD primer
RV primer
Probe / 5’-TCCAGAAGTCAGCGGCCT-3’
5’-CTGAGCCCGCAGTGTGG-3’
5’-TCAAGGTGGATGGCACCCAGGAT-3’
Acadm / FWD primer
RV primer
Probe / 5’-GGAAATGATCAACAAAAAAAGAAGTATTT-3’
5’-ATGGCCGCCACATCAGA-3’
5’-TGTCACACAGTAAGGACACATCATTGGCTG-3’
Acadvl / FWD primer
RV primer
Probe / 5’-ATCTCTGCCCAGCGACTTT-3’
5’-TTCTGGCTTGTCCAGAACTG-3’
5’-CTGAGTGGCCTCCCTGGCA-3’
Cpt1b / FWD primer
RV primer
Probe / 5’-TCTAGGCAATGCCGTTCAC-3’
5’-GAGCACATGGGCACCATAC-3’
5’-TCAAGCCGGTCATGGCACTGG-3’
Cpt2 / FWD primer
RV primer / 5’-AGTATCTGCAGCACAGCATCGTA-3’
5’-GGCTTCTGTGCACTGAGGTATCT-3’
Hk2 / FWD primer
RV primer / 5’-TGCTACAGGTCCGAGCCA-3’
5’-ATGCTGTCGTCACACGTGC-3’
Cycs / FWD primer
RV primer
Probe / 5’-ACCAAATCTCCACGGTCTGTT-3’
5’-GGATTCTCCAAATACTCCATCAG-3’
5’-ACAGATGCCAACAAGAACAAAGGCAT-3’
Cox 4 / FWD primer
RV primer
Probe / 5’-TACTTCGGTGTGCCTTCGA-3’
5’-TGACATGGGCCACATCAG-3’
5’-TAGTCTTCACTCTTCACAACACTCCCATGT-3
Atp5b / FWD primer
RV primer
Probe / 5’-CGTGAGGGCAATGATTTATACCAT-3’
5’-TCCTGGTCTCTGAAGTATTCAGCAA-3’
5’-ACCAACGCTACCTTGGAAGTGGCATCT-3
Nppa (ANF) / FWD primer
RV primer
Probe / 5’-AGTGCGGTGTCCAACACAGA-3’
5’-GACCTCATCTTCTACCGGCATCT-3’
5’-TCAAGAACCTGCTAGACCTGGAGGAG-3’
Nppb (BNP) / FWD primer
RV primer
Probe / 5’-GCTGCTTTGGGCACAAGATAG-3’
5’-GCAGCCAGGAGGTCTTCCTA-3’
5’-CAGTGCGTTACAGCCCAAACGA-3’
Myh6 / FWD primer
RV primer
Probe / 5’-GGTCCACATTCTTCAGGATTCTCT-3’
5’-CCTTCTCTGACTTTCGGAGGTACT-3’
5’-GGGCGTCCGTCATTCTGTCACTCAAAC-3’
Atp2a2 (SERCA2a) / FWD primer
RV primer
Probe / 5’-GGAGATGCACCTGGAAGACT-3’
5’-CCACACAGCCGACGAAA-3’
5’-TTCATCAAATACGAGACCAACCTGACT-3’
PGC-1α (Ppargc1a) / FWD primer
RV primer
Probe / 5’-CGGAAATCATATCCAACCAG-3’
5’-TGAGGACCGCTAGCAAGTTTG-3’
5’-TCATTCTCTTCATCTATCTTCTCAAATATGTTCGCAGG-3’
Pfk / FWD primer
RV primer
Probe / 5’-CGTTGAGGTAGGAATACTTCTGCA-3’
5’-ACCTCTTCCGAAAGGAGTGGA-3’
5’-TCGGAATGGTGATATCGATAACGACAC-3
Pdk4 / FWD primer
RV primer
Probe / 5’-CCGCTGTCCATGAAGCA-3’
5’-GCAGAAAAGCAAAGGACGTT-3’
5’-TGCTGGACTTTGGTTCAGAAAATG-3’
36B4 / FWD primer
RV primer / 5’-ATCCCTGACGCACCGCCGTGA-3’
5’-TGCATCTGCTTGGAGCCCACGTT-3
18s rRNA / FWD primer
RV primer / 5’-GGTTGATCCTGCCAGTAGCATAT-3’
5’-GCCATTCGCAGTTTCACTGTAC-3
Primers for quantification of Mt DNA
NADH dehydrogenase
Subunit 1 (mitochondrial) / FWD primer
RV primer / 5’-CCCATTCGCGTTATCTT-3’
5’-AAGTTGATCGTAACGGAAGC-3’
Lipoprotein Lipase
(genomic) / FWD primer
RV primer / 5’-GGATGGACGGTAAGAGTGATTC-3’
5’-ATCCAAGGGTAGCAGACAGGT-3’
Probes are 5'-FAM and 3'-TAMRA modified