Extended Data Fig. 3: Doxycycline does not promote cell survival in MELAS or ND1 cybrid cells through the integrated protein response (ATF4) or reported protein targets.
From: Tetracyclines promote survival and fitness in mitochondrial disease models
a, Western blot of integrated response proteins in MELAS cybrid cells treated with doxycycline (Dox) for 24 hours (n = 2 experiments). b, Western blot of ATF4 in siATF4 MELAS cybrid cells (n = 2 experiments). c, 48 hour low-glucose survival of siATF4 MELAS cybrid cells treated with doxycycline (n = 3 biologically independent samples). d, 48 hour low-glucose survival of MELAS cybrid cells treated with doxycycline with or without ISRIB (Integrated Stress Response Inhibitor) (n = 3 biologically independent samples over n = 2 independent experiments) e, 48 hour low-glucose survival of MELAS cybrid cells treated with pan matrix-metalloprotease (MMP) inhibitor BB-94 (n = 2 biologically independent samples). f, 4 day galactose survival assay of ND1 cybrid cells treated with BB-94 (n = 2 biologically independent samples). g, 48 hour low-glucose survival of MELAS cybrid cells treated with the PARP inhibitor Olaparib (n = 2 biologically independent samples). h, 4 day galactose survival of ND1 cybrid cells treated with Olaparib (n = 2 biologically independent samples). i, 48 hour low-glucose survival of MELAS cybrid cells treated with the PAR1 inhibitor Vorapaxar (n = 2 biologically independent samples). j, 8 day galactose survival of ND1 cybrid cells treated with Vorapaxar (n = 2 biologically independent samples). k, Western blot of PAR1 in siF2R MELAS cybrid cells (n = 2 experiments). l, 48 hour low-glucose survival of MELAS cybrid cells depleted of PAR1 (siF2R) (n = 3 biologically independent samples). Data are presented as mean values ± s.e.m. error bars, Student’s t-test with a two-stage linear step-up procedure of Benjamini, Krieger and Yekutieli, with Q = 5%, * q < 0.05.