Fig. 8.

Role of ATP-dependent SERCA2a/PLN and Drp1 in FBXL4-offered benefits in ‘double-damage’ cell model. A–F: Experiments depicting intracellular Ca²⁺ transient properties in control and ‘double damage’ (DD) mouse cardiomyocytes; G–J: Caffeine-induced changes in baseline fura-2 fluorescence intensity (FFI), ΔFFI and intracellular Ca²⁺ decay rate; K–M: Impact of SERCA inhibition using thapsigargin (Tg) on FBXL4-offered benefit against DD-induced intracellular Ca²⁺ mishandling including baseline Fura-2 fluorescent intensity; N–P: Effect of FBXL4 on DD-induced myocardial energy deficit using OCR curve (panel N), basal OCR and maximal respiration (panel O–P); and Q–S: Effect of Drp1 knock-in or knock-out in FBXL4-offered intracellular Ca²⁺ responses under DD challenge. Cardiomyocytes from WT, Drp1^CKI and Drp1^hetCKO mice were challenged with DD regimen for 12 h in the absence or presence of FBXL4 overexpression; Mean ± SEM, n = 6 mice per group (5 replicates per heart, panel B–F, K–S), n = 5 mice per group (3 replicates per heart, panel G–J). Statistical significance was estimated using one-way ANOVA followed by the Tukey's multiple comparison test or repeated measures ANOVA in R and Bonferroni adjusted test. ***p < 0.001, ****p < 0.0001 between indicated groups.