bims-mitrat 2025-02-23 papers

Semin Cancer Biol. 2025 Feb 13. pii: S1044-579X(25)00013-6. [Epub ahead of print]110 65-82

Metabolic crosstalk between platelets and cancer: Mechanisms, functions, and therapeutic potential.

Zhixue Chen, Lin Xu, Yejv Yuan, Si Zhang, Ruyi Xue.

Platelets, traditionally regarded as passive mediators of hemostasis, are now recognized as pivotal regulators in the tumor microenvironment, establishing metabolic feedback loops with tumor and immune cells. Tumor-derived signals trigger platelet activation, which induces rapid metabolic reprogramming, particularly glycolysis, to support activation-dependent functions such as granule secretion, morphological changes, and aggregation. Beyond self-regulation, platelets influence the metabolic processes of adjacent cells. Through direct mitochondrial transfer, platelets reprogram tumor and immune cells, promoting oxidative phosphorylation. Additionally, platelet-derived cytokines, granules, and extracellular vesicles drive metabolic alterations in immune cells, fostering suppressive phenotypes that facilitate tumor progression. This review examines three critical aspects: (1) the distinctive metabolic features of platelets, particularly under tumor-induced activation; (2) the metabolic crosstalk between activated platelets and other cellular components; and (3) the therapeutic potential of targeting platelet metabolism to disrupt tumor-promoting networks. By elucidating platelet metabolism, this review highlights its essential role in tumor biology and its therapeutic implications.

Keywords: Cancer therapy; Energy metabolism; Mitochondrial transfer; Platelet

DOI: https://doi.org/10.1016/j.semcancer.2025.02.001

J Strength Cond Res. 2025 Mar 01. 39(3): e427

Manuscript Clarification: Mitochondria Transplantation: Rescuing Innate Muscle Bioenergetic Impairment in a Model of Aging and Exercise Intolerance.

Mehryar Habibi Roudkenar, Nima Najafi-Ghalehlou, Amaneh Mohammadi Roushandeh.

DOI: https://doi.org/10.1519/JSC.0000000000005034

J Strength Cond Res. 2025 Mar 01. 39(3): e428

Response to Manuscript Clarification: Mitochondria Transplantation: Rescuing Innate Muscle Bioenergetic Impairment in a Model of Aging and Exercise Intolerance.

Tasnim Arroum, James D McCully, Maik Hüttemann, Moh H Malek.

DOI: https://doi.org/10.1519/JSC.0000000000005035

Adv Mater. 2025 Feb 17. e2500303

Mitochondrial Transplantation via Magnetically Responsive Artificial Cells Promotes Intracerebral Hemorrhage Recovery by Supporting Microglia Immunological Homeostasis.

Mi Zhou, Jinhui Zang, Yuxuan Qian, Qiang Zhang, Yifan Wang, Tingting Yao, Hongyu Yan, Kai Zhang, Xiaojun Cai, Lixian Jiang, Yuanyi Zheng.

The immune-inflammatory responses in the brain represent a key therapeutic target to ameliorate brain injury following intracerebral hemorrhage (ICH), where pro-inflammatory microglia and its mitochondrial dysfunction plays a pivotal role. Mitochondrial transplantation is a promising strategy to improve the cellular mitochondrial function and thus modulate their immune properties. However, the transplantation of naked mitochondria into the brain has been constrained by the peripheral clearance and the difficulty in achieving selective access to the brain. Here, a novel strategy for mitochondrial transplantation via intravenous injection of magnetically responsive artificial cells (ACs) are proposed. ACs can protect the loaded mitochondria and selectively accumulate around the lesion under an external magnetic field (EMF). In this study, mitochondria released from ACs can effectively improve microglial mitochondrial function, attenuate their pro-inflammatory attributes, and elevate the proportion of immunosuppressive microglia. In this way, microglia immune homeostasis in the brain is reestablished, and inflammation is attenuated, ultimately promoting functional recovery. This study presents an effective approach to transplant mitochondria into the brain, offering a promising alternative to modulate the immune-inflammatory cascade in the brain following ICH.

Keywords: artificial cells; immune homeostasis; intracerebral hemorrhage; magnetic drug targeting; mitochondrial transplantation

DOI: https://doi.org/10.1002/adma.202500303

Nat Commun. 2025 Feb 20. 16(1): 1803

Zika virus NS1 drives tunneling nanotube formation for mitochondrial transfer and stealth transmission in trophoblasts.

Rafael T Michita, Long B Tran, Steven J Bark, Deepak Kumar, Shay A Toner, Joyce Jose, Indira U Mysorekar, Anoop Narayanan.

Zika virus (ZIKV) is unique among orthoflaviviruses in its vertical transmission capacity in humans, yet the underlying mechanisms remain incompletely understood. Here, we show that ZIKV induces tunneling nanotubes (TNTs) in placental trophoblasts which facilitate transfer of viral particles, proteins, mitochondria, and RNA to neighboring uninfected cells. TNT formation is driven exclusively via ZIKV non-structural protein 1 (NS1). Specifically, the N-terminal 1-50 amino acids of membrane-bound ZIKV NS1 are necessary for triggering TNT formation in host cells. Trophoblasts infected with TNT-deficient ZIKVΔTNT mutant virus elicited a robust antiviral IFN-λ 1/2/3 response relative to WT ZIKV, suggesting TNT-mediated trafficking allows ZIKV cell-to-cell transmission camouflaged from host defenses. Using affinity purification-mass spectrometry of cells expressing wild-type NS1 or non-TNT forming NS1, we found mitochondrial proteins are dominant NS1-interacting partners. We demonstrate that ZIKV infection or NS1 expression induces elevated mitochondria levels in trophoblasts and that mitochondria are siphoned via TNTs from healthy to ZIKV-infected cells. Together our findings identify a stealth mechanism that ZIKV employs for intercellular spread among placental trophoblasts, evasion of antiviral interferon response, and the hijacking of mitochondria to augment its propagation and survival and offers a basis for novel therapeutic developments targeting these interactions to limit ZIKV dissemination.

DOI: https://doi.org/10.1038/s41467-025-56927-2