2026-10-12T17:40:40Z https://www.scidb.cn/oai

10.57760/sciencedb.39624 2026-06-12T14:12:59Z

2026-06-12 Disrupting Mitochondrial Homeostasis Via TBC1D15 Protein doi:10.57760/sciencedb.39624 en Background: Mitochondria–lysosome coupling and mitophagy are indispensable for mitochondrial homeostasis. Existing studies confirm TBC1D15 participates in organelle crosstalk, but whether its total expression or subcellular trafficking dominates mitochondrial quality control remains unclear. This study aimed to clarify the regulatory pattern of TBC1D15 trafficking and distinguish divergent mechanisms of CCCP and gold nanoparticles (AuNPs) targeting TBC1D15 in mitochondrial regulation. Methods: PC-12 neuronal cells and HeLa epithelial cells were treated with gradient-concentration AuNPs, mitochondrial uncoupler CCCP and autophagy inhibitor chloroquine. PINK1 was knocked down via specific siRNA transfection. Western blotting was used to detect mitophagy-related proteins, and subcellular fractionation was performed to analyze the subcellular distribution of TBC1D15 between mitochondria and lysosomes. Results: Impaired TBC1D15 translocation from mitochondria to lysosomes destroyed organelle contact and induced mitochondrial dysfunction. High-dose AuNPs retained TBC1D15 on mitochondria and interrupted its lysosomal delivery independent of PINK1, while CCCP regulated TBC1D15 abundance via canonical PINK1-dependent mitophagy. Low-concentration AuNPs upregulated TBC1D15 and promoted physiological mitochondria–lysosome interaction, showing obvious biphasic concentration-dependent bioeffects. Conclusions: TBC1D1-mediated inter-organelle trafficking, instead of overall cellular protein level, serves as a core modulator of mitochondrial homeostasis. High-concentration AuNPs can work as a specific functional blocker of TBC1D15, offering a potential therapeutic candidate for diseases caused by PINK1-pathway deficiency-related mitochondrial damage. Mitochondria; TBC1D15; Mitochondrial homeostasis; Lysosomes Zhang Xiwei PUBLIC https://creativecommons.org/licenses/by-nc-nd/4.0/ dataset Science Data Bank