Fig. 1: The absence of neurofibromin decreases protein levels and enzymatic activity of respiratory complex I.

OXPHOS protein levels were analyzed by Western immunoblot (WB, A) or blue native polyacrylamide gel electrophoresis (BN-PAGE, B). In A, calnexin was used as a loading control. In B, bands corresponding to different respiratory complexes were cut, run on an SDS-PAGE and probed for the expression of the complex I subunits NDUFB8, GRIM19, NDUFS1 and NDUFS3, of the complex V α subunit, of the complex III UQCRC2 subunit and of the complex II SDHB subunit. C Spectrophotometric analysis of the NADH dehydrogenase activity of complex I (CI) is shown as arbitrary units and normalized for citrate synthase (CS) activity. D BN-PAGE carried out on digitonized mitochondria to preserve assembled respiratory supercomplexes. Gels were either subjected to in gel complex I activity, or stained with Coomassie blue and transferred to PVDF membrane for protein identification. UQCRC1 and GRIM19 are complex III and complex I subunits, respectively. E Spectrophotometric analysis of the NADH dehydrogenase activity of complex I in control (empty vector, EV) and GRD Nf1−/− MEFs in basal condition (10 % FBS) or following growth in a media containing PDGF (10 ng/ml, and 0.5 % FBS). All experiments in the Figure were carried out in Nf1+/+ and Nf1−/− MEFs. Data are reported as mean ± SD values (n ≥ 3); ***p < 0.001; **p < 0.01; *p < 0.05 with a Student’s t test analysis.