Desipramine-induced lysosomal vacuolization is independent of autophagy.

Desipramine, a commonly used antidepressant drug, induced cytosolic vacuolization in L929 cells. The level of LC3-II was elevated and that of p62 was reduced in desipramine-treated L929 cells, indicating the induction of autophagy by desipramine. Surprisingly, massive vacuolization was observed in desipramine-treated L929 cells in the presence of LY294002, an inhibitor of autophagy. On the other hand, bafilomycin A1, an inhibitor of vacuolar type H+ ATPase, almost completely inhibited vacuolization in desipramine- or desipramine/LY294002-treated L929 cells. Furthermore, desipramine-induced vacuolization was observed in autophagy-deficient Atg7-/- mouse embryonic fibroblasts (MEFs) as well as wild-type Atg7+/+ MEFs. These results demonstrate that desipramine-induced lysosomal vacuolization is independent of autophagy.