In vivo up-regulation of the unfolded protein response after hypoxia

► We monitored the UPR in liver and myocardium, tissues that differ in O2 requirement. ► Mice exposure to 6.5% O2 resulted in ATF4, CHOP and GADD34 activation in liver. ► In the myocardium the ATF4-CHOP-GADD34 markers were not detectably activated. ► The apoptotic pathway mediated by CHOP and p-JNK was activated in hepatocytes only. ► Hepatocytes and myocites fine tune the UPR signaling pathway in in vivo hypoxia.