The disulfide bridge formed between HMGB1 cysteines and beclin-1 is an essential conformation structure required for sustained autophagy.115 Furthermore, HMGB1 controls the checkpoint process that proceed to autophagy, via preventing the calpain-mediated cleavage of autophagic regulator beclin-1 and ATG5 during inflammation.116,117 Though autophagy level was downregulated proportionally according to severity of sepsis condition, injection of cell-permeable TAT-beclin-1 successfully restore mitochondrial biogenesis and preserve sepsis cardiac function via PINK1/Parkin and AMPK/ULK1 signaling. The gene discussed is BECN1; the disease is Sepsis.