bims-mitrat 2026-03-22 papers

Cell Rep Methods. 2026 Mar 13. pii: S2667-2375(26)00038-X. [Epub ahead of print] 101338

MitoTracker transfers from astrocytes to neurons independently of mitochondria.

Katriona L Hole, Rosalind Norkett, Emma Russell, Patrick Cottilli, Molly Strom, Jack H Howden, Nicola J Corbett, Janet Brownlees, Michael J Devine.

The neuroprotective transfer of mitochondria from astrocytes to neurons has been primarily investigated by labeling astrocytic mitochondria with the dye MitoTracker. Here, we labeled astrocytic mitochondria with both a genetically encoded fluorophore (GFP) and MitoTracker dye and then imaged neurons immediately after co-culture with astrocytes or astrocyte-conditioned media (ACM). We report that MitoTracker transfers to neurons from both astrocytes and ACM, independently of mitochondrial transfer. Our observations provide an essential caveat to the use of this reagent and suggest that the investigation of astrocyte-neuron mitochondrial transfer, and other systems in which contact-independent transfer has been reported, requires the use of alternative labeling techniques.

Keywords: CP: cell biology; CP: neuroscience; MitoTracker; astrocyte; intercellular mitochondrial transfer; mitochondria; neuron

DOI: https://doi.org/10.1016/j.crmeth.2026.101338

Eur J Neurosci. 2026 Mar;63(6): e70463

Mobile Powerhouses: Mitochondria Transfer via Tunnelling Nanotubes in Brain Health and Neurodegenerative Diseases.

Anna Henrich, Hannah Scheiblich.

Mitochondria are central regulators of cellular metabolism, calcium homeostasis and survival. Owing to the brain's exceptional energy demand, mitochondrial dysfunction is tightly linked to neurodegenerative and neuroinflammatory disorders. Recent evidence challenges the traditional view of mitochondria as strictly cell-autonomous organelles, revealing that they can be exchanged between cells via intercellular transfer by extracellular vesicles, gap junctions or tunnelling nanotubes (TNTs) as part of an adaptive mechanism of metabolic support and signalling. Among the pathways mediating this intercellular exchange, TNTs-thin, actin-rich cytoplasmic bridges-have emerged as key conduits for mitochondrial transfer in the nervous system. TNTs enable bidirectional exchange of mitochondria between neurons, glia and vascular cells, thereby promoting bioenergetic recovery after injury and modulating immune and inflammatory responses. This review summarizes current evidence for TNT-mediated mitochondrial transfer in the brain and highlights the underlying molecular mechanisms that coordinate mitochondrial movement, including cytoskeletal dynamics, mitochondrial trafficking machinery and stress-induced signalling cascades. While mitochondrial donation can restore metabolic balance and promote neuroprotection, it may also facilitate the spread of pathological proteins, contributing to disease progression. Understanding the underlying molecular mechanism of TNT-mediated mitochondrial transfer provides a new framework for exploring metabolic communication and cellular resilience in the brain. By emphasizing emerging conceptual and mechanistic insights, we outline how advancing this field could pave the way for the development of innovative therapeutic strategies for neurodegenerative and neuroinflammatory disorders.

Keywords: Miro1/2; actin dynamics; cell–cell connectivity; cytoskeletal remodelling; intercellular communication

DOI: https://doi.org/10.1111/ejn.70463

J Control Release. 2026 Mar 15. pii: S0168-3659(26)00220-8. [Epub ahead of print]393 114818

Pomegranate-inspired bionic microgel/periosteum composite harnessing reactive oxygen species for immune-engineered bone regeneration.

Ziyi Feng, Meiqi Jin, Minhao Li, Jia Guo, Shu Guo, Huazhe Yang, Xiaoting Sun.

Excessive reactive oxygen species (ROS) and unresolved inflammation create a hostile microenvironment that compromises regeneration in critical-sized bone defects. Here, we developed a pomegranate-inspired bionic microgel/periosteum composite (PBC) featuring a hierarchical "membrane-seed" modular design, in which a periosteum-mimetic PDA/PLLA membrane provided not only ROS counteraction but also a continuous protective interface and defect compartmentalization. Conductive GelMA/PEDOT:PSS microgels serving as the "seeds" enabled enhanced and prolonged ROS clearance as well as conformal filling of irregular geometries, and increased cell-material contact. The PBC system was shown to possess adequate mechanical, electro-chemical and anti-ROS properties as well as high biocompatibility. In an inflammatory environment, the PBC enabled macrophage polarization toward reparative phenotype, remarkable ROS clearance and osteogenic differentiation, which were further enhanced under electrical stimulation. Transcriptomic analyses together with Seahorse measurements indicated that PBC remodelled energy metabolism of macrophages, and intercellular mitochondrial transfer was observed as a potential contributory route in macrophage-osteoblast coupling-based bone regeneration. In a rat critical-sized mandibular defect model, PBC implantation improved bone formation and defect bridging and was accompanied by moderated early inflammatory signals. Collectively, the PBC system provided a modular periosteal substitute integrating structural biomimicry with sustained redox buffering and immune-informed regeneration.

Keywords: Anti-oxidation; Bone defect repair; Conductive hydrogels; Macrophage polarization; Mitochondria transfer; Mitochondrial metabolism

DOI: https://doi.org/10.1016/j.jconrel.2026.114818

Cell. 2026 Mar 18. pii: S0092-8674(26)00230-8. [Epub ahead of print]

Transplantation of encapsulated mitochondria alleviates dysfunction in mitochondrial and Parkinson's disease models.

Mitochondrial transplantation holds significant potential for the treatment of mitochondrial diseases. However, how to efficiently deliver exogenous mitochondria to somatic cells or tissues remains unresolved. We present a mitochondrial transplantation approach to deliver mitochondria into the cells and tissues of mice and monkeys with high efficiency, based on encapsulating mitochondria with vesicles derived from the plasma membrane of erythrocytes. Treatment with encapsulated mitochondria complemented the loss, deletion, or mutation of mitochondrial DNA, thereby rescuing the associated bioenergetic and biochemical defects in patient-derived cells with mitochondrial disorders. Furthermore, mitochondrial capsules rescued the mitochondrial DNA depletion syndrome and Leigh syndrome in Dguok-/- and Ndufs4-/- mouse models, respectively. Moreover, in a mouse model of Parkinson's disease, mitochondrial capsules rescued neuron loss, improved motor skills, and restored mitochondrial function in the affected brain regions. Our study demonstrates the potential of this mitochondrial capsule as a treatment for mitochondrial disorders and proposes an "organelle therapy" strategy in regenerative medicine.

Keywords: Parkinson’s disease; degenerative disease; extracellular vesicle; mitochondria; mitochondrial diseases; mitochondrial transfer; mtDNA depletion syndrome; mtDNA mutation; organelle therapy

DOI: https://doi.org/10.1016/j.cell.2026.02.023