bims-mitrat 2026-11-15 papers

ACS Appl Bio Mater. 2026 Nov 12.

Poly(N-isopropylacrylamide)-Grafted Hyaluronic Acid Semi-Gels for Localized Mitochondrial Transplantation in Spinal Cord Injuries.

A Jamie Ahmed, Krithika Iyer, Davis Anum, Sajeev Kaur, Maria F Zapata-Jaramillo, Patrick G Sullivan, Jason E DeRouchey, Thomas D Dziubla, Samir P Patel.

Mitochondrial transplantation (MT) represents a promising strategy for treating conditions associated with mitochondrial dysfunction, including neurodegenerative diseases, metabolic syndromes, and tissue regeneration scenarios such as spinal cord injury (SCI). Unlike conventional approaches that address symptoms, MT aims to restore cellular energy homeostasis by replacing impaired mitochondria with functional organelles. However, clinical translation has been limited by the short extracellular lifetime of isolated mitochondria and by their rapid dispersion from the injection site. To address these barriers, we developed a thermoresponsive carrier based on hyaluronic acid covalently grafted with poly(N-isopropylacrylamide) (HA-PNIPAAm), which combines the biocompatibility and bioactivity of HA with the temperature-induced chain collapse of PNIPAAm. The copolymers form injectable semi-gels that thicken above the transition temperature, resist dispersion under flow, and dissolve over hours to release their cargo. We characterized their composition, phase transition behavior, viscoelasticity, and mitochondrial release kinetics, and showed that encapsulation preserved mitochondrial respiratory function and membrane potential relative to free mitochondria over the time window relevant to delivery. In a rat contusion SCI model, subdural delivery of mitochondria in HA-PNIPAAm semi-gels restored spinal cord mitochondrial respiration to uninjured levels at 48 h post-injury. These findings establish HA-PNIPAAm semi-gels as a tunable, injectable platform for localized, cell-compatible mitochondrial delivery and support further evaluation of MT for SCI and other conditions characterized by mitochondrial dysfunction.

Keywords: hyaluronic acid; injectable semi-gel; mitochondrial transplantation; spinal cord injury; thermoresponsive copolymers

DOI: https://doi.org/10.1021/acsabm.6c01366

Int J Mol Sci. 2026 Nov 03. pii: 9837. [Epub ahead of print]27(21):

Restoring Bioenergetics in the Traumatized Eye: The Emergence of Mitochondrial Implantation as a Treatment for Acute Ocular Injury.

Emma Peveri, Daniella Beiner, Andrew J W Huang, Jian-Xing Ma, Amish Asthana, Anthony Atala, Giuseppe Orlando, Yuanyuan Zhang.

Acute ocular injuries-such as chemical burns, ischemic insults, and mechanical trauma-frequently lead to irreversible vision loss by triggering rapid intracellular adenosine triphosphate (ATP) depletion, mitochondrial calcium overload, severe oxidative stress, and profound mitochondrial dysfunction. Current clinical management primarily focuses on suppressing inflammation and preventing secondary infection, but it fails to address the underlying bioenergetic collapse that drives cellular degeneration. While stem cell and extracellular vesicle therapies have been widely investigated, direct mitochondrial transplantation has recently emerged as a novel strategy for metabolic rescue. This review evaluates the therapeutic potential of exogenously administered mitochondria to mitigate mitochondrial dysfunction and acute trauma in the eye. Emerging preclinical studies demonstrate that transplanted mitochondria can be internalized by selected ocular cell types, conferring short-term cytoprotection, preserving retinal ganglion cell viability, and accelerating corneal epithelial repair. However, robust evidence regarding long-term mitochondrial integration, functional fusion, durable metabolic rescue, and clinical efficacy remains limited. Despite critical challenges in delivery, stability, and dosing, mitochondrial transplantation represents a promising frontier in regenerative ophthalmology that directly targets bioenergetic failure to preserve vision.

Keywords: acute ocular injury; bioenergetic failure; metabolic rescue; mitochondrial transplantation; ocular trauma

DOI: https://doi.org/10.3390/ijms27219837

Ecotoxicol Environ Saf. 2026 Nov 10. pii: S0147-6513(26)01370-9. [Epub ahead of print]326 121040

Spring pollen from the Mongolian Plateau amplifies macrophage inflammation through mitochondrial transfer from damaged nasal epithelium.

Zhiqiang Jiang, Caiyan An, Mingyang Shan, Yanfei Li, Lixin Wang, Junjing Zhang, Ling Zhao.

Pollen is a prevalent environmental bioaerosol and allergen. To investigate its cytotoxicity and mechanisms, human nasal epithelial cells (HNEpC) and THP-1-derived macrophages were exposed to spring pollen from the Mongolian Plateau at environmentally relevant concentrations (1-100X ambient; 1X = 3.5 µg/cm²). Cell viability was measured by CCK-8. Mitochondrial function was assessed by JC-1, MitoSOX, 8-OHdG, and Seahorse XF analysis. Mitochondrial transfer was traced with MitoTracker and quantified by flow cytometry. NLRP3 inflammasome activation was determined by Western blot. THP-1 viability remained > 75% up to 100X pollen, whereas HNEpC viability decreased significantly at 20X and above (P < 0.05). At 10X pollen, HNEpC showed reduced mitochondrial membrane potential, dynamic mROS changes (peaking at 12 h), increased mitochondrial 8-OHdG, suppressed oxidative phosphorylation, and enhanced glycolysis (P < 0.05). In co-culture, the proportion of double-positive THP-1 cells containing HNEpC-derived mitochondria increased from 2.78% ± 0.17-46.72% ± 2.23% after 72 h of pollen exposure, and this increase was reduced to 8.33% ± 1.25% by the EV secretion inhibitor GW4869 (P < 0.05). Pollen exposure upregulated NLRP3, ASC, PRO-CASPASE-1, IL-1β, and IL-18, and increased cleaved CASPASE-1 (p20) and cleaved IL-1β (p17) in THP-1 macrophages; these effects were blocked by the NLRP3 inhibitor MCC950 (P < 0.05). These data indicate that pollen induces mitochondrial damage in HNEpC and promotes potential EV-associated mitochondrial transfer to macrophages, leading to metabolic reprogramming and NLRP3-dependent inflammatory activation.

Keywords: Airway inflammation; Metabolic reprogramming; Mitochondrial transfer; NLRP3; Pollen

DOI: https://doi.org/10.1016/j.ecoenv.2026.121040

Curr Opin Neurobiol. 2026 Nov 12. pii: S0959-4388(26)00124-8. [Epub ahead of print]101 103288

Mitochondria on the move: Mitochondrial release and transfer in nervous system health and disease.

Tessa Onraet, Steven Zuryn.

While studies of mitochondria in the nervous system traditionally focus on their roles as key energy producers, mitochondria are increasingly recognised as essential determinants of nervous system development, function, and disease. The conventional understanding of mitochondria places them within the confines of individual neurons and glial cells, where they support nervous system function and remain steadfast against cellular threats. However, emerging research is redefining the properties of mitochondria as highly dynamic modulators of the nervous system that can be released or transferred between neurons and glia as active repair or signalling effectors or for targeted glia-based degradation. Here, we discuss recent key reports of this dynamic transfer of mitochondria in the context of nervous system health and disease.

DOI: https://doi.org/10.1016/j.conb.2026.103288