a, Immunoblot analysis of 786-O cells with indicated genotype upon
anoxic condition for 16 h or treated with 1 mM DMOG for 8 h. n = 3 biological
independent experiments. b, Immunoblot analysis of 786-O cells with
indicated VHL status transduced with lentiviral pL.KO shRNA targeting
EGLN1 (shE1), EGLN2 (shE2),
EGLN3 (shE3) or no targeting control (shSCR). n = 3
biological independent experiments. c, Fluorescence images of 786-O
cells with indicated VHL status transduced with lentiviral pL.KO shRNA targeting
EGLN3 or no targeting control. Mitochondria are visualized
by MitoTracker Red staining. Corresponding flow cytometry analysis of
MitoTracker Green-stained 786-O cells is shown in d. Data are
presented as mean values ± SD. One way ANOVA Tukey's Multiple
Comparison Test. ****p <0.0001. n = 3 biological independent experiments.
e, Immunoblot analysis of mouse superior cervical ganglia (SCG)
(left), adrenal gland medulla (right) of indicated genotype. n = 4 biologically
independent EGLN3 wildtype or knockout mice. f,
Immunoblot analysis of mouse heart of indicated genotype. n=3 biologically
independent EGLN3 wildtype or knockout mice. g,
Left: Fluorescence images of primary EGLN3 MEFs of indicated
genotype stably transduced with lentivirus encoding EGLN3 WT,
catalytic death mutant EGLN3-H196A or empty control.
Mitochondria are visualized by MitoTracker Red staining. Right: Corresponding
flow cytometry analysis of MitoTracker Green-stained primary MEFs cells of
indicated genotype stably transduced with lentivirus encoding
EGLN3 WT, catalytic death mutant
EGLN3-H196A or empty control. n = 3 biological independent
experiments. Data are presented as mean values ± SD. One way ANOVA
Tukey's Multiple Comparison Test. ****p <0.0001. Corresponding
immunoblot of primary EGLN3 MEFs is shown in h. n
= 3 biological independent experiments. i, Aged, 56-60 weeks old KO
mice reach exhaustion significantly earlier and perform less work at comparable
performed power (WT n=16, KO n=15 independent biological samples per genotype,
male mice). Data are presented as mean values ± SD. Two-tailed unpaired t
test. p =0.014, p =0.0318.