Recent studies have shown that mitochondria derived damage associated molecular pattern molecules (mtDAMP) are increased in the blood circulation of patients suffering from severe injuries and sepsis. DAMP’s (including mitochondrial DNA and proteins) are considered to be pro-inflammatory and one of the important mediators of ongoing systemic inflammation during sepsis. The mechanism of mtDAMP release during sepsis is currently enigmatic. In this regards, the recent paper by Kana et al. [1] in Autophagy shows that upon lipopolysaccharide stimulation of primary hepatic cells, active extracellular release of mtDAMP occurs through the exocytosis of autolysosomes. Inhibition of the autophagy process attenuated the mtDAMP release from the cells. These data demonstrate the active role of autophagy in secretion of cellular proteins from the cells during inflammatory conditions like sepsis. This paper provides important insight into the mechanism of sepsis induced mtDAMP release and provides background for future investigations.