Pathological cardiac hypertrophy, the adaptive response of the myocardium to various pathological stimuli, is one of the primary predictors and predisposing factors of heart failure. However, its molecular mechanisms underlying pathogenesis remain poorly understood. Here, we studied the function of Samm50 in mitophagy during Ang II-induced cardiomyocyte hypertrophy via lentiviruses mediated knockdown and overexpression of Samm50 protein. We first found that Samm50 is a key positive regulator of cardiac hypertrophy, for western blot and real-time quantitative PCR detection revealed Samm50 was downregulated both in pressure-overload-induced hypertrophic hearts and Ang II-induced cardiomyocyte hypertrophy. Then, Samm50 overexpression exhibits enhanced induction of cardiac hypertrophy marker genes and cell enlargement in primary mouse cardiomyocytes by qPCR and immunofluorescence analysis, respectively. Meanwhile, Samm50 remarkably reduced Ang II-induced autophagy as indicated by decreased mitophagy protein levels and autophagic flux, whereas the opposite phenotype was observed in Samm50 knockdown cardiomyocytes. However, the protective role of Samm50 deficiency against cardiac hypertrophy was abolished by inhibiting mitophagy through Vps34 inhibitor or Pink1 knockdown. Moreover, we further demonstrated that Samm50 interacted with Pink1 and stimulated the accumulation of Parkin on mitochondria to initiate mitophagy by co-immunoprecipitation analysis and immunofluorescence. Thus, these results suggest that Samm50 regulates Pink1-Parkin-mediated mitophagy to promote cardiac hypertrophy, and targeting mitophagy may provide new insights into the treatment of cardiac hypertrophy.

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ObjectiveGlutamine fructose-6-phosphate transaminase 2 (GFPT2) is involved in a wide range of biological functions in human cancer. However, few studies have comprehensively analyzed the correlation between GFPT2 and different cancer prognoses and tumor microenvironments (TMEs).MethodsWe evaluated the expression level and prognostic value of GFPT2 using updated public databases and multiple comprehensive bioinformatics analysis methods and explored the relationship between GFPT2 expression and immune infiltration, immune neoantigens, tumor mutational burden (TMB), and microsatellite instability in pan-cancer.ResultsGFPT2 was highly expressed in five cancers. GFPT2 expression correlates with the prognosis of several cancers from The Cancer Genome Atlas (TCGA) and is significantly associated with stromal and immune scores in pan-cancer. High GFPT2 expression in BLCA, BRCA, and CHOL was positively correlated with the infiltration of immune cells, such as B-cells, CD4+ T, CD8+ T cells, dendritic cells, neutrophils, and macrophages.ConclusionHigh GFPT2 expression may modify the outcomes of patients with BLCA, BRCA, or CHOL cancers by increasing immune cell infiltration. These findings may provide insights for further investigation into GFPT2 as a potential target in pan-cancer.