Figure 4
Toll-like receptor 9 (TLR9) decreases the mitochondrial ATP synthesis by altering [Ca2+]m via SERCA2.
A, B Time-lapse analysis of mitochondrial matrix Ca2+ in G-CaMP2-mt-transfected cardiomyocytes after the vehicle control (n = 25; circle) or CpG-ODN (n = 20; triangle) administration. CpG administration significantly reduced mitochondrial Ca2+ in cardiomyocytes. Representative images with pseudocolour for each condition are shown in (A).
C Adenovirus-mediated transfection of mit-ATeam showed mitochondrial localization in rat cardiomyocytes, which enabled to monitor the mitochondrial ATP levels.
D Time-lapse analysis of mitochondrial ATP levels in mit-ATeam-transfected cardiomyocytes after the vehicle control (n = 13; circle), CpG-ODN (n = 11; triangle) or oligomycin (n = 11; square), an inhibitor of ATP synthase used as a positive control. Mitochondrial ATP levels significantly dropped after CpG stimulation in cardiomyocytes.
E Schematic presentation of two different TLR9 signalling pathways. Cardiomyocytes or neurons sense DNA (danger signal) upon tissue injury, reduce energy metabolism by alteration of microdomain Ca2+ handling through SERCA2 and consequently increase the stress tolerance through AMPK activation, while immune cells initiate the inflammatory response.
Data information: Scale bars indicate 10 ÎĽm. Error bars indicate s.e.m. **P < 0.01 ***P < 0.001 compared with the control.
Source data are available online for this figure.
