TBC1D15 Expression Indicates the Toxicity of Gold Nanoparticles on Mitochondria in PC-12 Cells

Gold nanoparticles (AuNPs) have long been considered to be one of the safest central nervous system (CNS) drug delivery carriers. However, recent studies have shown that AuNPs can affect the mitochondria–lysosome interaction in neuronal cells, although the underlying mechanism is not fully understood. The mitochondria–lysosome interaction is crucial for mitochondrial damage repair and quality control. In this study, we used PC-12 cells as a neuronal cell model to investigate the impact of AuNPs on the regulation of mitochondria–lysosome interaction. We found that AuNPs disrupt this regulation by interfering with the expression of TBC1D15, a key regulator of the mitochondria–lysosome interaction. Specifically, the expected increase in TBC1D15 expression upon mitochondrial damage was reduced with increasing AuNP concentrations. Concurrently, we observed a significant increase in the number of mitochondria and the level of the mitochondria–lysosome interaction. Additionally, the level of cellular autophagy represented by LC3B was markedly enhanced. These findings suggest that AuNPs may lead to the accumulation of mitochondrial damage by interfering with TBC1D15, resulting in neurotoxicity. This study provides important theoretical support for elucidating the mechanism of AuNP-mediated disruption of the mitochondria–lysosome interaction, which is crucial for understanding the potential risks of using AuNPs as drug delivery carriers in the central nervous system.