Polystyrene nanoplastics impair mitochondrial function, quality control, and ER-mitochondria crosstalk in HeLa cells.
4 affiliations
- 1Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Caserta, Italy.
- 2Institute of Crystallography, CNR, Caserta, Italy.
- 3Department of Human Sciences, Link Campus University, Roma, Italy.
- 4Institute for Polymers, Composites and Biomaterials, CNR, Pozzuoli, Italy.
Abstract
Introduction
Polystyrene nanoplastics (PS-NPs) represent persistent environmental contaminants derived from the degradation of plastic debris and are increasingly detected in biological systems, raising concerns regarding their potential effects on human health. Emerging evidence suggests that, following cellular internalization, PS-NPs can induce intracellular stress responses and interfere with mitochondrial homeostasis, highlighting mitochondria as key targets of nanoplastic-induced cellular dysfunction. This study aimed to investigate the effects of PS-NPs on mitochondrial function in HeLa cells. Particular attention was devoted to Mitochondrial Quality Control (MQC) pathways, including the mitochondrial Unfolded Protein Response (UPRmt), a stress-adaptive mechanism that remains poorly characterized in response to nanoplastic exposure in human cellular model. In addition, the study examined the functional crosstalk between the Endoplasmic Reticulum and mitochondria.Methods
HeLa cells were exposed to PS-NPs, and mitochondrial bioenergetics, oxidative stress, mitochondrial membrane potential, cellular ATP levels, extracellular lactate levels, and calcium homeostasis were assessed using functional assays. MQC-related pathways, including UPRmt, mitochondrial biogenesis, dynamics, autophagy/mitophagy, and ER stress responses, were evaluated through biochemical, molecular, and imaging approaches.Results
Our results demonstrate that PS-NP exposure induces mitochondrial dysfunction, characterized by impaired mitochondrial coupling, mitochondrial membrane depolarization, increased H₂O₂ levels in cell lysates, and altered cellular redox homeostasis. Moreover, PS-NPs disrupt MQC processes, leading to an imbalance in the mechanisms that maintain mitochondrial homeostasis, including modulation of UPRmt-associated proteins and dysregulation of ER-mitochondria communication via Mitochondria-Associated Membranes (MAMs).Conclusion
Collectively, these data advance our understanding of PS-NP toxicity by identifying alterations in MQC systems and ER-mitochondria crosstalk as key events in nanoplastic-induced cellular stress. These findings provide novel mechanistic insights into nanoplastic toxicity and highlight the potential impact of environmental PS-NP exposure on cellular homeostasis and human health.
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BibTeX
@article{petito2026polystyrene,
title = {{Polystyrene nanoplastics impair mitochondrial function, quality control, and ER-mitochondria crosstalk in HeLa cells.}},
author = {Giuseppe Petito and Maria Teresa Gentile and Arianna Cuomo and Angelo Fusco and Sara Falvo and Maria Della Valle and Gianluca D'Abrosca and Carla Isernia and Roberto Fattorusso and Maria Emanuela Errico and Antonia Lanni and Gaetano Malgieri and Rosalba Senese},
journal = {Frontiers in toxicology},
year = {2026},
month = oct,
doi = {10.3389/ftox.2026.1907794},
url = {https://europepmc.org/article/MED/42898481},
note = {CC BY},
}
RIS
TY - JOUR
TI - Polystyrene nanoplastics impair mitochondrial function, quality control, and ER-mitochondria crosstalk in HeLa cells.
AU - Giuseppe Petito
AU - Maria Teresa Gentile
AU - Arianna Cuomo
AU - Angelo Fusco
AU - Sara Falvo
AU - Maria Della Valle
AU - Gianluca D'Abrosca
AU - Carla Isernia
AU - Roberto Fattorusso
AU - Maria Emanuela Errico
AU - Antonia Lanni
AU - Gaetano Malgieri
AU - Rosalba Senese
PY - 2026
DA - 2026/10/05
JO - Frontiers in toxicology
DO - 10.3389/ftox.2026.1907794
UR - https://europepmc.org/article/MED/42898481
AB - Introduction Polystyrene nanoplastics (PS-NPs) represent persistent environmental contaminants derived from the degradation of plastic debris and are increasingly detected in biological systems, raising concerns regarding their potential effects on human health. Emerging evidence suggests that, following cellular internalization, PS-NPs can induce intracellular stress responses and interfere with mitochondrial homeostasis, highlighting mitochondria as key targets of nanoplastic-induced cellular dysfunction. This study aimed to investigate the effects of PS-NPs on mitochondrial function in HeLa cells. Particular attention was devoted to Mitochondrial Quality Control (MQC) pathways, including the mitochondrial Unfolded Protein Response (UPRmt), a stress-adaptive mechanism that remains poorly characterized in response to nanoplastic exposure in human cellular model. In addition, the study examined the functional crosstalk between the Endoplasmic Reticulum and mitochondria.Methods HeLa cells were exposed to PS-NPs, and mitochondrial bioenergetics, oxidative stress, mitochondrial membrane potential, cellular ATP levels, extracellular lactate levels, and calcium homeostasis were assessed using functional assays. MQC-related pathways, including UPRmt, mitochondrial biogenesis, dynamics, autophagy/mitophagy, and ER stress responses, were evaluated through biochemical, molecular, and imaging approaches.Results Our results demonstrate that PS-NP exposure induces mitochondrial dysfunction, characterized by impaired mitochondrial coupling, mitochondrial membrane depolarization, increased H₂O₂ levels in cell lysates, and altered cellular redox homeostasis. Moreover, PS-NPs disrupt MQC processes, leading to an imbalance in the mechanisms that maintain mitochondrial homeostasis, including modulation of UPRmt-associated proteins and dysregulation of ER-mitochondria communication via Mitochondria-Associated Membranes (MAMs).Conclusion Collectively, these data advance our understanding of PS-NP toxicity by identifying alterations in MQC systems and ER-mitochondria crosstalk as key events in nanoplastic-induced cellular stress. These findings provide novel mechanistic insights into nanoplastic toxicity and highlight the potential impact of environmental PS-NP exposure on cellular homeostasis and human health.
SN - 2673-3080
ER -