ML405/85 mimic TRAP1 actions on mitochondrial respiratory chain enzymes and metabolites
(A) Treatment with ML405 inhibits phosphorylation of transiently expressed mitochondria-targeted c-Src at Tyr-416 (p-Y416) but has no effect on total mitochondrial c-Src (Input) in ARPE cells. The blot shown is representative of four independent experiments.
(B) Densitometry of phospho-c-Src bands in (A) normalized to total c-Src (Input).
(C and D) ML405/85 inhibit complex II (SDH) activity of the mitochondrial respiratory chain in purified ARPE mitochondria (C), which results in the expected increase in cellular succinate levels (D). TTFA: thenoyltrifluoroacetone, complex II inhibitor (positive control).
(E) Treatment with ML405 lowers COX activity in purified ARPE mitochondria.
(F) Treatment with ML405/85 increase cellular and secreted lactate levels in ARPE cells. Data are represented as the mean ± SD ∗∗∗p < 0.0005, ∗∗p < 0.001.