BAX has been shown to translocate to lysosomes where it is suggested to trigger LMP and cell death under different pathophysiological conditions, including Parkinson’s disease, oxidative stress, and autophagic cell death (35–37). To assess BAX translocation to the lysosomal membrane and its colocalization with RECS1, we detected active BAX using the 6A7 conformational antibody. Analysis of RECS1 (using the Flag antibody) and the distribution of the lysosomal protein LAMP-2 in MEFs indicated that under basal conditions (no RECS1), BAX remained mainly cytosolic (fig. S4H). However, BAX colocalized with RECS1 in LAMP-2–positive vesicles following RECS1 induction (Fig. 3, E to G). After CQ treatment, BAX was redistributed into large LAMP-2–positive vesicles, an effect that was dependent on RECS1 expression (Fig. 3E). Active BAX was present preferentially in Flag-RECS1–positive lysosomes in cells treated with CQ (Fig. 3, F and G). Together, these results suggest that RECS1 induces cell death through LMP in response to lysosomal stress, correlating with the translocation of BAX to lysosomes
Overexpression of RECS1 in CQ-stressed cells causes LMP and translocation of BAX to the lysosome, which induces cell death. BAX is a proapoptotic protein.