Perfluorooctane sulfonate induces ferroptosis-dependent non-alcoholic steatohepatitis via autophagy-MCU-caused mitochondrial calcium overload and MCU-ACSL4 interaction.

The incidence of nonalcoholic steatohepatitis (NASH) is related with perfluorooctane sulfonate (PFOS), yet the mechanism remains ill-defined. Mounting evidence suggests that ferroptosis plays a crucial role in the initiation of NASH. In this study, we used mice and human hepatocytes L-02 to investigate the role of ferroptosis in PFOS-induced NASH and the effect and molecular mechanism of PFOS on liver ferroptosis.

Exosomal miR-181a-2-3p derived from citreoviridin-treated hepatocytes activates hepatic stellate cells trough inducing mitochondrial calcium overload.

Increasing evidences indicate the vital role of exosomes-mediated intercellular communication in the pathogenesis of liver fibrosis. However, the underlying mechanisms are still not clearly defined. In this study, we found that citreoviridin (CIT), a mycotoxin and ectopic ATP synthase (e-ATPS) inhibitor, induced liver fibrosis in mice.

Perfluorooctane sulfonate induces mitochondrial calcium overload and early hepatic insulin resistance via autophagy/detyrosinated alpha-tubulin-regulated IP3R2-VDAC1-MICU1 interaction.

Perfluorooctane sulfonate (PFOS), one kind of persistent organic pollutants, is associated with insulin resistance (IR) in general population. However, the exact mechanism is still obscure. In this study, we found that 50 μM PFOS caused IR in L-02 hepatocytes after 1 h, and induced autophagy and mitochondrial calcium (Ca) accumulation as early as 0.

Insight of the role of mitochondrial calcium homeostasis in hepatic insulin resistance.

Due to the rapid rise in the prevalence of chronic metabolic disease, more and more clinicians and basic medical researchers focus their eyesight on insulin resistance (IR), an early and central event of metabolic diseases. The occurrence and development of IR are primarily caused by excessive energy intake and reduced energy consumption. Liver is the central organ that controls glucose homeostasis, playing a considerable role in systemic IR.

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.

The existence and function of mitochondrial component in extracellular vesicles.

Intercellular transfer of mitochondria and mitochondrial components through extracellular vesicles (EVs), including microvesicles and exosomes, is an area of intense interest. The cargos that are carried by EVs define their biological activities. Mitochondria are in charge of bioenergetics and maintenance of cell viability.