a, Mitochondrial respiration reflected by oxygen consumption rate
(OCR) of 786-O cells with indicated genotype was monitored using the Seahorse
XF-96 Extracellular Flux Analyzer with the sequential injection of oligomycin (1
μM), FCCP (1 μM), and rotenone/antimycin (0.5 μM).
b-c, The measurement of oxygen consumption rate (OCR) of 786-O
cells with indicated VHL status transduced with lentiviral pL.KO shRNA targeting
EGLN3 or no targeting control (b), primary
EGLN3+/+ and EGLN3-/- MEFs (c) stably
transduced with lentivirus encoding EglN3 WT, catalytic death mutant or empty
control (d). a-d, data are presented as mean values ± SD. n
= 3 biological independent experiments. e, Crystal violet staining
of 786-O cells with indicated VHL status treated with high glucose (25 mM) or no
glucose (0 mM) respectively for 36 hours. Corresponding ADP/ATP ratio is shown
in (h). f, Crystal violet staining of 786-O cells with
indicated VHL status treated with 100 μM 3-bromopyruvic acid (3-BP) for 4
hours. Corresponding ADP/ATP ratio is shown in (i). g, Crystal
violet staining of 786-O cells with indicated VHL status treated with 25
μM gossypol for 36 hours. Corresponding ADP/ATP ratio is shown in
(j). h-j, data are presented as mean values ± SD. One
way ANOVA Tukey's Multiple Comparison Test. *p <0.05, ****p
<0.0001. n = 3 biological independent experiments. k,
Crystal violet staining of 786-O cells with indicated VHL status treated with 5
μM PKA inhibitor H89 for 24 hours, prior to glucose deprivation for 36
hours. Corresponding ADP/ATP ratio is shown in (n). l,
Crystal violet staining of 786-O cells treated with 5 μM PKA inhibitor
H89 for 24 hours, prior to 100 μM 3-BP treatment for 4 hours.
Corresponding ADP/ATP ratio is shown in (o). m,
Crystal violet staining of 786-O cells treated with 5 μM PKA inhibitor
H89 for 24 hours, prior to 25 μM gossypol for 36 hours. Corresponding
ADP/ATP ratio is shown in (p). n-p, data are presented as mean
values ± SD. One way ANOVA Tukey's Multiple Comparison Test. *p
<0.05, ****p <0.0001. n = 3 biological independent
experiments.