Perfluorooctane Sulfonate Induces Autophagy-Dependent Lysosomal Membrane Permeabilization by Weakened Interaction Between Tyrosinated Alpha-Tubulin and Spinster 1

Perfluorooctane sulfonate (PFOS) is one kind of persistent organic pollutants. In previous study, we found that PFOS induced autophagy-dependent lysosomal membrane permeabilization (LMP) in hepatocytes, and siRNA against lysosomal permease spinster 1 (SPNS1) relieved PFOS-induced LMP. However, whether and how SPNS1 functioned as the link between autophagy and LMP was still not defined. In this study, we constructed a stable cell line expressing high levels of SPNS1. We found that SPNS1 interacted specifically with α-tubulin of tyrosinated isotype by pull-down assay. After treatment with PFOS, the level of tyrosinated α-tubulin was autophagy-dependently decreased. SPNS1-tyrosinated α-tubulin interaction was disrupted subsequently, which led to LMP eventually. We also found that stable high-expression of SPNS1 in hepatocytes accelerated lysosomal acidification, and deteriorated PFOS-induced LMP. This study pointed out that SPNS1-tyrosinated α-tubulin interaction mediated the cross-talk between autophagy and LMP induced by PFOS, shedding new light on the mechanism of PFOS hepatotoxicity.