Fig. 3. Rapamycin does not substantially alter mitochondrial function or complex I assembly.
(A and B) FK-506 delivered at the highest tolerated dose (see fig. S8) failed to enhance survival (A) or attenuate disease (B) in Ndufs4−/− mice. (C) Rapamycin has no observed effect on respiratory activity or complex I deficiency of mitochondria isolated from ~50-day-old Ndufs4−/− mice; n = 4 to 6 mice per data point. (see also fig. S10). (D) Native-in-gel activity assays reveal that rapamycin does not influence assembly or stability of complex I (see also fig. S11). (E and F) Complex I subunits (NDUFS3 and NDUFS9) are significantly reduced in Ndufs4−/− mice, and rapamycin has no effect on their total levels (F) or subcellular localization (E) in brain. Levels of other mitochondrial proteins (cytochrome c, the complex IV subunit COXIV, and HSP60) are independent of both Ndufs4 genotype and treatment (see also fig. S9). *P < 0.05,**P < 0.005, Student’s t test; ns, not significant. Error bars are ±SEM.