bims-cytox1 2025-12-07 papers

Clin Exp Pharmacol Physiol. 2026 Jan;53(1): e70098

COX17 Attenuates Diabetes-Associated Retinal Injury by Improving Mitochondrial Function.

Hai-Yan Lian, Zhen-De Deng, Ming Yan, Zhen Huang, Ya Ye, Yan-Ping Song.

PURPOSE: Diabetic retinopathy (DR), a common complication of diabetes, is a leading cause of blindness globally. Cytochrome C oxidase copper chaperone (COX17) is important for Cytochrome C oxidase assembly, and COX17 overexpression is reported to improve mitochondrial function in renal tissue. This study aimed to explore whether COX17 alleviated DR by regulating mitochondrial function.
METHODS: Diabetes was induced in rats by a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Overexpression of COX17 was performed by infection of adeno-associated virus into the vitreous body of rats 2 weeks after STZ injection. Human retinal microvascular endothelial cells (HRMECs) were cultured with high-glucose (HG) medium (20 mM d-glucose). Immunofluorescence assay, enzymatic histochemistry assay, CCK-8 assay, DCFH-DA staining, flow cytometry, western blot, and real-time PCR were performed.
RESULTS: COX17 expression was decreased in the retinal tissues of diabetic rats and HG-stimulated HRMECs. COX17 overexpression alleviated retinal neovascularisation and increased retinal thickness in diabetic rats. COX17 overexpression decreased ROS and apoptosis and increased Cytochrome C oxidase activity, mtDNA copy number, ATP content, and mitochondrial membrane potential (MMP) in both the retinal tissues of diabetic rats and HG-induced HRMECs. Overexpression of COX17 effectively reduced cell apoptosis and increased cell viability. Overexpression of COX17 increased mtDNA in HG-induced HRMECs.
CONCLUSIONS: Overall, our study suggested that COX17 overexpression exerted protective effects in the retinas of diabetic rats and in HRMECs by stabilising mitochondrial function.

Keywords: COX17; HRMECs; ROS; diabetic retinopathy; mitochondria

DOI: https://doi.org/10.1111/1440-1681.70098

Nat Commun. 2025 Dec 04. 16(1): 10898

Cytochrome c oxidase dependent respiration is essential for T cell activation, proliferation and memory formation.

Tatiana N Tarasenko, Emily Warren, Bharati Singh, Amanda Fuchs, Jose Marin, Marten Szibor, Christopher King, Peter J McGuire.

T cell activation requires extensive metabolic reprogramming, but the specific requirement for mitochondrial respiration (MR) remains unresolved. While most studies have focused on aerobic glycolysis as the primary driver of proliferation and effector function, the role of MR has not been completely defined. To isolate MR from proton pumping by cytochrome c oxidase (COX), we expressed the non-proton-pumping alternative oxidase (AOX) in activated COX-deficient T cells. AOX restored electron flow, membrane potential, and mitochondrial ATP production, ultimately rescuing proliferation, effector and memory differentiation, and antiviral immunity. These improvements required upstream electron input, particularly from Complex I, with Complex II and DHODH contributing more modestly. Despite restored MR, glycolysis remained elevated, likely due to altered redox signaling. These findings demonstrate that MR, normally mediated by COX, is necessary and can be sufficient to support T cell activation and function, independent of proton translocation, provided upstream electron input is maintained.

DOI: https://doi.org/10.1038/s41467-025-65910-w

Pestic Biochem Physiol. 2026 Jan;pii: S0048-3575(25)00477-8. [Epub ahead of print]216(Pt 1): 106764

Multi-omics analyses identify the modulators COX6A1 and NAL as regulators of silk cocoon formation in Plutella xylostella.

Rui-Chang Niu, Qing-Hui Zeng, Wen-Jing Wang, Jia Hu, Tong-Xian Liu, Shi-Ze Zhang.

The diamondback moth (DBM) is a major global pest of cruciferous crops. Silk production, essential for DBM larval locomotion and pupal attachment, is governed by fibroin heavy chain (FibH), fibroin light chain (FibL), and fibrohexamerin (P25). However, the regulatory mechanisms and downstream key genes involved in silk production in DBM remain poorly understood. To address this, we integrated transcriptomic and proteomic data from CRISPR/Cas9 generated PxFibH, PxFibL, and PxP25 mutants to investigate the impact of silk gene deletions in the silk gland and identify modulators of silk formation. In the transcriptomic analysis, we identified 1994, 913, and 1266 differentially expressed genes (DEGs) in the three mutant strains, respectively. GO and KEGG enrichment analysis revealed significant involvement in pathways such as oxidation-reduction process, transmembrane transport, enzyme activity, and extracellular matrix (ECM) receptor interaction. At the proteomic level, 604, 210, and 266 differentially expressed proteins (DEPs) were identified in the three mutants, respectively. GO and KEGG enrichment analysis of these DEPs consistently highlighted energy metabolism, hydrolase activity, and catalytic activity pathways. Integrated multi-omics analyses identified three conserved regulator genes: cytochrome c oxidase subunit 6A1 (COX6A1), N-acetylneuraminate lyase (NAL), and protein phosphatase 1 regulatory subunit 14B (PPP1R14B). CRISPR/Cas9 knockout of PxCOX6A1 resulted in incomplete cocoon formation, along with increased larval mortality, prolonged development, and reduced oviposition. PxNAL knockout was lethal, while heterozygotes exhibited decreased cocoon formation, pupal weight, and fecundity. This study reveals FibH/FibL/P25-dependent metabolic networks regulating silk production and identifies COX6A1 and NAL as novel targets for environmentally sustainable pest control strategies.

Keywords: CRISPR/Cas9; Cytochrome c oxidase subunit 6A1; Omics; Pest control; Plutella xylostella

DOI: https://doi.org/10.1016/j.pestbp.2025.106764