Endotoxin Engages Mitochondrial Quality Control via an iNOS-Reactive Oxygen Species Signaling Pathway in Hepatocytes

Figure 4

mtROS signaling following LPS stimulation is required for induction of mitochondrial quality control pathways in hepatocytes. In hepatocyte culture, Nrf2 expression following LPS stimulation is abrogated by both the iNOS inhibitor 1400 W (10 nM) and the mitochondrial ROS scavenger MitoTEMPO (5 μM, 12 h LPS exposure, (a)). Induction of the mitochondrial biogenesis regulatory genes Pgc-1α, Nrf1, and Tfam as measured by qRT-PCR following 12 h LPS exposure was suppressed by co-culture with MitoTEMPO (5 μM), suggesting a partial dependence on mtROS (b). mtROS scavenging with MitoTEMPO (1 mg/kg) in vivo also abrogates appropriate induction of both PGC-1α and LC3 following LPS administration (12-hour exposure, (c)). compared to untreated controls; ^# compared to LPS-treated alone.

(a)

(b)

(c)