Consistent with this notion, the depletion of autophagic proteins, such as LC3B and Beclin 1, causes accumulation of dysfunctional mitochondria and cytosolic release of mtDNA, leading to enhanced secretion of IL-1β and IL-18 in macrophages.244 Upon pressure overload, lysosomal deoxyribonuclease (DNase) II deficiency in cardiomyocytes leads to mtDNA accumulation in autolysosomes, which subsequently activates TLR9 signaling-mediated inflammatory responses, contributing to heart failure.254 Accordingly, enhancement of mitophagy can put the brakes on inflammatory responses. The gene discussed is BECN1; the disease is heart failure.