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Impt-1 expression in impt-1 +/– mutants and worms exposed to impt-1 RNAi. (a,b) Impt-1 mRNA expression in day 0 N2 (n = 3 pools of 150 worms) and impt-1 +/– (ok3233) (n = 3 pools of 150 worms) worms (a) or N2 worms treated with L4440 (control) (n = 3 pools of 150 worms) or impt-1 RNAi (n = 3 pools of 150 worms) from eggs (b). Data are presented as mean ± SEM and compared using unpaired Student t test, **P = 0.0097 in comparison to N2, *P = 0.036 in comparison to L4440. The experiments were performed once in triplicate. Raw data in Additional file 11: Table S2. (PDF 296 kb)

Lifespan increase induced by krs-1 RNAi is blocked in gcn-1 mutants. Lifespan assay of N2 worms and gcn-1(nc40) mutants treated with L4440 or krs-1 RNAi from day 0 adults. Values of median lifespan and statistics are reported in Additional file 10: Table S1. Survival curves were compared using the log-rank test. Data demonstrate the composite of experiments XXXVI and XXXVII. (PDF 146 kb)

SKN-1 and DAF-16 target gene expression upon impt-1 RNAi. (a) Average integrated density of GFP expression of the Pgst-4::GFP reporter at different larval stages [L1 (L4440, n = 19; impt-1, n = 20), L2 (L4440, n = 36; impt-1, n = 29), L4 (L4440, n = 23; impt-1, n = 31); Student t test). This is a composite of two independent experiments. (b) Representative images of Pgst-4::GFP expression in L2 larvae treated with L4440 (control) or impt-1 RNAi from L1. Dashed lines delimitate the body of the worm. Head and tail are indicated by arrows. (c) Average integrated density of GFP expression of the Psod-3::GFP reporter at different larval stages [L1 (L4440, n = 9; impt-1, n = 12), L2 (L4440, n = 18; impt-1, n = 24), L4 (L4440, n = 14; impt-1, n = 12); *P

Tissue-specific impt-1 RNAi in intestine, muscle, or neurons is not sufficient to increase lifespan. (a–c) Lifespan assays of worms with tissue-specific RNAi sensitivity in intestine (a), muscle (b), or neurons (c). The worms were treated with L4440 (control) or impt-1 RNAi from L1. Values of median lifespan and statistics are reported in Additional file 10: Table S1. Survival curves were compared using the long-rank test. All experiments were repeated three times. Data demonstrate the composite of experiments XXIII–XXV (a), XXVI–XXVIII (b), or XXIX–XXXI (c). (PDF 52 kb)

Impt-1 expression in response to DR or aging. (a) Impt-1 mRNA expression in N2 worms and worms carrying the daf-16(m26), skn-1(zu135), and hsf-1(sy441) mutations. These genes are necessary for some protocols of DR to extend lifespan in C. elegans. (b) Impt-1 mRNA expression in N2 worms and eat-2 (DR model) on days 0 and 10. n = 3 pools of at least 150 worms per group. Data are presented as mean ± SEM and compared using a one-way ANOVA with Dunnet post-hoc (a) or two-way ANOVA (b). The experiments were performed once in triplicate. *P

Impt-1 interactions with components of the DR pathway to control longevity. (a,b) Lifespan assays of aak-2(n48) and hsf-1(sy441) mutants treated with L4440 (control) or impt-1 RNAi from L1. (c–f) Lifespan assays of N2 worms and impt-1 +/– (ok3233) mutants treated with aak-2, let-363, hsf-1, or atf-5 RNAi from day 0 adults. Values of median lifespan and statistics are reported in Additional file 10: Table S1. Survival curves were compared using the log-rank test. All experiments were repeated at least twice. Data demonstrate the composite of experiments XI–XIII (a, b), XV–XVII (c), XIV–XVII (d), XIV, XV, XVII (e) and XVIII, XIX (f). (PDF 243 kb)

Phenotypic characterization of N2 worms treated with impt-1 RNAi from L1. (a) Developmental timing after egg laying of N2 and gcn-2(ok871) worms (N2 L4440 RNAi, n = 469; N2 impt-1 RNAi, n = 510; gcn-2 L4440 RNAi, n = 365; gcn-2 impt-1 RNAi, n = 411; P

Impt-1 knockdown promotes stress resistance. (a, b) Lifespan assays under heat stress (28 °C) of N2 worms and impt-1 +/– (ok3233) mutants (a) or N2 worms treated with L4440 (control) or impt-1 RNAi from L1 (b). Values of median lifespan and statistics are reported in Additional file 10: Table S1. Survival curves were compared by log-rank test. Experiment (a) was repeated three times and (b) was performed once. Data demonstrate the composite of experiments XXXII–XXXIV (a) or the experiment XXXV (b). (c) Fraction of dead N2, impt-1 +/– (ok3233) and gcn-2(ok871) worms when exposed to 5 mM or 7.5 mM sodium arsenite for 7 hours (N2, n = 44; impt-1 +/– , n = 46; gcn-2, n = 48; *P

Compilation of lifespan data. (DOCX 51 kb)

The ability to respond to fluctuations of reactive oxygen species (ROS) within the cell is a central aspect of mammalian physiology. This dynamic process depends on the coordinated action of transcriptional factors to promote the expression of genes encoding for antioxidant enzymes. Here, we demonstrate that the transcriptional coregulators, PGC-1 alpha and NCoR1, are essential mediators of mitochondrial redox homeostasis in skeletal muscle cells. Our findings reveal an antagonistic role of these coregulators in modulating mitochondrial antioxidant induction through Sod2 transcriptional control. Importantly, the activation of this mechanism by either PGC-1 alpha overexpression or NCoR1 knockdown attenuates mitochondrial ROS levels and prevents cell death caused by lipid overload in skeletal muscle cells. The opposing actions of coactivators and corepressors, therefore, exert a commanding role over cellular antioxidant capacity.