Cadmium promotes nonalcoholic fatty liver disease by inhibiting intercellular mitochondrial transfer.

Mitochondrial transfer regulates intercellular communication, and mitochondria regulate cell metabolism and cell survival. However, the role and mechanism of mitochondrial transfer in Cd-induced nonalcoholic fatty liver disease (NAFLD) are unclear. The present study shows that mitochondria can be transferred between hepatocytes via microtubule-dependent tunneling nanotubes. After Cd treatment, mitochondria exhibit perinuclear aggregation in hepatocytes and blocked intercellular mitochondrial transfer. The different movement directions of mitochondria depend on their interaction with different motor proteins. The results show that Cd destroys the mitochondria-kinesin interaction, thus inhibiting mitochondrial transfer. Moreover, Cd increases the interaction of P62 with Dynactin1, promotes negative mitochondrial transport, and increases intracellular lipid accumulation. Mitochondria and hepatocyte co-culture significantly reduced Cd damage to hepatocytes and lipid accumulation. Thus, Cd blocks intercellular mitochondrial transfer by disrupting the microtubule system, inhibiting mitochondrial positive transport, and promoting their negative transport, thereby promoting the development of NAFLD. Highlights: Mitochondrial transfer between hepatocytes can be achieved through microtubule-dependent tunneling nanotubes Cadmium inhibits the intercellular mitochondrial transfer Inhibition of intercellular mitochondrial transfer mediates cadmium-induced nonalcoholic fatty liver disease. Motor protein-dependent mitochondrial mobility is a target for cadmium to inhibit intercellular mitochondrial transfer [ABSTRACT FROM AUTHOR]