bims-cytox1 2025-12-21 papers

J Biol Chem. 2025 Dec 17. pii: S0021-9258(25)02922-9. [Epub ahead of print] 111070

The cytochrome c oxidase subunit COX6B1 is required for redox-sensitive early assembly and late stabilization of complex IV.

Kristýna Čunátová, Marek Vrbacký, Michal Knězů, Alena Pecinová, Lukáš Alán, Josef Houštěk, Erika Fernández-Vizarra, Tomáš Mráček, Petr Pecina.

COX6B1 is a nuclear-encoded subunit of the human mitochondrial cytochrome c oxidase (cIV) located in its intermembrane space-facing region. The relevance of COX6B1 in mitochondrial physiopathology was highlighted by the missense pathogenic variants associated with cIV deficiency. Despite the assigned COX6B1 role as a late incorporation subunit, the COX6B1 human cell line knock-out (KO) exhibited a total loss of cIV. To get a deeper insight into the mechanisms driving the lack of cIV assembly or destabilization in the absence of COX6B1, we used the COX6B1 KO cell background to express alternative oxidase and COX6B1 pathogenic variants. These analyses uncovered that the COX6B1 subunit is indispensable for redox-sensitive early cIV assembly steps, besides its contribution to the stabilization of cIV in the late assembly stages. In addition, we have evidenced the incorporation of partially assembled cIV modules directly into supercomplex structures, supporting the 'cooperative assembly' model for respiratory chain biogenesis.

Keywords: COX; COX6B1; COX6B2; OXPHOS assembly; alternative oxidase; cIV; complex IV; cytochrome c oxidase; mitochondrial deficiency; respiratory chain supercomplexes

DOI: https://doi.org/10.1016/j.jbc.2025.111070

J Biophotonics. 2025 Dec 15. e202500374

A Label-Free Hyperspectral Imaging Device for Ex Vivo Characterization and Grading of Meningioma Tissues.

Pietro Ricci, Camilla Bonaudo, Ivan Ezhov, Anam Toaha, Dorotea Nardini, Manuel Camelia, Federica Lucidi, Filippo Nozzoli, Tim Mach, Ilias Tachtsidis, Daniel Rueckert, Alessandro Della Puppa, Luca Giannoni, Francesco S Pavone.

Histopathology remains the gold standard for definitive tumor diagnosis after surgical resection; however, its lengthy processing time can delay critical postoperative care. Hyperspectral imaging (HSI) is emerging as a promising label-free technique for rapid biochemical tissue assessment. Here, we present HyperProbe1.1 (HP1.1), an HSI system designed for noninvasive analysis of fresh brain tumor biopsies. In this proof-of-concept study, we applied the HP1.1 system to freshly excised meningioma specimens-the most common primary intracranial tumors. The platform enabled rapid, label-free mapping of metabolic activity and vascular heterogeneity, while spectral unmixing further allowed the quantification of endogenous biomarkers such as cytochrome c oxidase (CCO), hemoglobin derivatives, and lipids, revealing molecular patterns consistent with histopathological tumor grading according to the 2021 WHO classification. These results highlight the feasibility of HSI for rapid biochemical tissue assessment and its potential integration into intraoperative decision-making.

Keywords: Hyperspectral Imaging; Meningiomas; Tumor Grade Discrimination

DOI: https://doi.org/10.1002/jbio.202500374

J Stroke Cerebrovasc Dis. 2025 Dec 17. pii: S1052-3057(25)00305-2. [Epub ahead of print] 108529

Dl-3-n-butylphthalide Protects against Ischemic Stroke by Enhancing Mitochondrial Function via MT-CO1 Upregulation.

Yangfang An, Biao Wang, Jiali Zhao, Hui Zhou, Qiong Zhou.

OBJECTIVE: Mitochondrial dysfunction is a key determinant of neuronal death and a promising therapeutic target in ischemic stroke. Dl-3-n-butylphthalide (NBP), an approved neuroprotective agent in China, has been shown to improve mitochondrial integrity, yet its precise molecular mechanisms remain unclear. This study aimed to determine whether NBP exerts neuroprotection by upregulating mitochondrial cytochrome c oxidase subunit 1 (MT-CO1) and to clarify the contribution of MT-CO1 to mitochondrial function recovery.
METHODS: MT-CO1 expression was measured in the circulation from acute ischemic stroke participants before and following NBP therapy. In SH-SY5Y cells under OGD/R treatment, the action of NBP on mitochondrial bioenergetics, oxidative stress, and apoptosis were assessed. MT-CO1 knockdown was used to determine mechanistic involvement.
RESULTS: NBP significantly increased MT-CO1 expression both in vivo and in vitro, improved mitochondrial membrane voltage and ATP production, reduced ROS generation, and decreased apoptosis. MT-CO1 silencing markedly attenuated these protective effects.
CONCLUSION: NBP protects against ischemia-induced mitochondrial dysfunction partly through MT-CO1 upregulation, supporting MT-CO1 as a potential therapeutic target for mitochondrial function protection in ischemic stroke.

Keywords: 3P medicine; MT-CO1; NBP; ischemic stroke; mitochondrial function; mitochondrial medicine; oxidative stress

DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2025.108529