Nanoplastic exposure induces mitochondrial dysfunction–driven inflammation and senescence in renal tubular epithelial cells

Mitochondrial damage was associated with activation of STING-dependent inflammatory signaling; pharmacological inhibition of STING attenuated inflammatory responses but did not suppress NP-induced cellular senescence, indicating mechanistic dissociation between inflammation and senescence. In contrast, prolonged NP exposure induced robust cellular senescence linked to sustained mitochondrial dysfunction. Activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) restored mitochondrial function and suppressed both inflammatory signaling and cellular senescence in vitro.

Importantly, pharmacological activation of PGC1α in NP-exposed mice mitigated mitochondrial damage, renal inflammation, senescence, and fibrotic remodeling in vivo. Collectively, these findings identify mitochondrial dysfunction as a central driver of NP-induced renal inflammation and senescence and provide mechanistic insight into the hazardous effects of NP exposure on the kidney.