FIGURE 1

Cardiomyocyte‐specific overexpression of tfeb alleviated bag3 cardiomyopathy phenotypes and restored impaired proteostasis. (A–C) Bright‐field images of dissected hearts (A) confirmative images of transmission electron microscope (TEM) (B) and quantification analysis (C) show enlarged ventricular surface area (VSA) normalized to body weight (BW), impaired sarcomere structure (Asterisks), and mitochondrial swelling (Arrows) phenotypes in the bag3^e2/e2 mutant hearts, which were ameliorated by Tg(cmlc2:tfeb), a cardiomyocyte‐specific tfeb overexpression transgenic line. Scale bars in A, 1 mm; in B, 20 μm. (D, E) Ejection fraction (EF) (D) and Survival (in %) (E) of bag3^e2/e2; Tg(cmlc2:tfeb) double mutant/transgenic fish compared to the bag3^e2/e2 single mutant, Tg(cmlc2:tfeb) single transgenic or WT control fish; n = 39–45, log‐rank test. (F) Quantitative RT‐PCR analysis of cardiomyopathy molecular markers in bag3^e2/e2; Tg(cmlc2:tfeb) double mutant/transgenic fish compared to single‐mutant/transgenic fish and WT control fish. n = 3 biological replicates, one‐way ANOVA. (G–H) Western blot (G) and quantification analysis of the LC3 II and ubiquitinated proteins in indicated fish heart treated with or without 50 nM bafilomycin A1 (BafA1) for 4 h. n = 4 biological replicates, one‐way ANOVA.