We can't find the internet
Attempting to reconnect
Something went wrong!
Hang in there while we get back on track
Comparative Analysis of Ultrafine Particulate Matter, Black Carbon, and Polystyrene Nanoplastics Identifies Mitochondrial Stress Adaptation as a Conserved Mechanism of Immunotoxicity
Summary
Tiny pollution particles, from air pollution soot and even nanoplastics, all stress out the "power plants" inside our immune cells (mitochondria) in a similar way, triggering inflammation that could contribute to disease. Each type of particle does this on its own timeline: soot from combustion causes long-lasting cell damage, while nanoplastics cause a milder but still persistent stress response. This matters because it suggests a shared biological pathway behind the health harms of air pollution and plastic pollution, and it points scientists toward specific molecules that could one day be used to detect this damage early or develop treatments to protect against it.
Abstract Several studies have been conducted on human exposure to ultrafine particulate matter (UFPM), Black carbon (BC), and polystyrene nanoplastics (PS-NPs). However, it remains unclear whether different chemical types of environmental nanoparticles induce a similar mitochondrial stress response or a unique particle-specific response. In the present study, we examined the molecular mechanisms underlying nanoparticle-induced mitochondrial stress response and immunotoxicity using human peripheral blood mononuclear cells exposed to UFPM, BC, and PS-NPs under similar experimental conditions. Oxidative stress, mitochondrial adaptation, respiratory chain integrity, mitochondrial integrated stress response, inflammatory signaling, and systems-level interactions between molecules were analyzed through the evaluation of the expression of NRF2, HIF-1α, PGC-1α, TFAM, OMA1, DELE1, mitochondrial ND1, Complex I-V, NF-κB, TNF-α, and NLRP3 and the use of principal component analysis, hierarchical clustering, and correlation networks. All three nanoparticles caused oxidative stress and mitochondrial dysfunction with different kinetics and mechanisms. UFPM mostly induced an acute antioxidant response and mitochondrial adaptation; BC led to chronic mitochondrial dysfunction, chronic activation of the OMA1-DELE1-mediated mitochondrial ISR pathway, and inflammation; while PS-NPs induced low but chronic mitochondrial adaptation along with mitochondrial biogenesis and stress responses. Our systems-level analysis showed that oxidative stress, mitochondrial adaptation, mitochondrial ISR, and inflammation represent a highly connected molecular network regardless of the physicochemical nature of the nanoparticles, with the OMA1- DELE1 axis being a key regulatory node connecting mitochondrial stress response and inflammation. Overall, we have found that mitochondrial stress response is a common mechanism underlying the toxicity of chemically different nanoparticles and have also revealed particle-specific stress-response dynamics responsible for the degree and persistence of cellular damage. The current work presents novel insights into the molecular mechanisms of nanoparticle-induced immunotoxicity and suggests OMA1, DELE1, NRF2, PGC-1α, TFAM, ND1, and Complex I-V as potential biomarkers.