bims-cytox1 2026-09-13 papers

on Cytochrome oxidase subunit 1

Issue of 2026–09–13
two papers selected by
Gavin McStay, Liverpool John Moores University

Dual role of HIF-1α in gliomas: enhancing COX7A2 degradation and SCAF1 expression for ATP production and tumor progression.
Comprehensive functional testing in fibroblasts has strong utility to diagnose mitochondrial disease.

Am J Cancer Res. 2026 ;16(8): 3338-3358

Dual role of HIF-1α in gliomas: enhancing COX7A2 degradation and SCAF1 expression for ATP production and tumor progression.

Minfang Lai, Wenping Feng, Jinyou Ouyang, Jianguo Kuang, Shengze Deng.

   OBJECTIVE: To investigate whether HIF-1α promotes SCAF1/COX7A2 replacement in complex IV and thereby influences glioma progression.
METHODS: A172 and U251 cells were subjected to CoCl2-induced hypoxia. The effects of hypoxia on cell behavior were assessed via CCK-8 for viability and Transwell for migration and invasion. Stable cell lines overexpressing HIF-1α, SCAF1, or CLPP, or knocking down COX7A2, LONP1, or CLPP were established. Mitochondrial supercomplex composition was analyzed by Blue Native PAGE. HIF-1α's binding to the SCAF1 promoter was validated by ChIP and dual-luciferase assays. Protein interactions were examined by Co-IP and GST pull-down. Xenograft tumor growth experiments conducted in nude mice was evaluated following COX7A2 overexpression or SCAF1 knockdown in tumor growth.
RESULTS: CoCl2 treatment significantly increased cell viability, migration, invasion, ATP concentration and the formation of I+III2+IV of glioma cells, and similar effects were observed upon HIF-1α overexpression, COX7A2 knockdown, or SCAF1 overexpression. HIF-1α targeted the SCAF1 promoter to regulate its expression, and HIF-1α regulated COX7A2 protein levels through LONP1 and CLPP. In the tumorigenesis experiment in nude mice, SCAF1 knockdown reduced tumor volume and weight, while COX7A2 overexpression reduced tumor volume and weight.
CONCLUSION: Hypoxia in glioma cells enhances cell viability, migration, invasion, ATP production, and I+III2+IV supercomplex formation, with HIF-1α regulating SCAF1 and COX7A2 levels. These findings highlight the promising potential of targeting the HIF-1α/SCAF1/COX7A2 pathway as a treatment option for glioma treatment.

Keywords:  ATP production; COX7A2; Hypoxia; SCAF1; glioma; oxidative phosphorylation

DOI:  https://doi.org/10.62347/RIKY8807
EMBO Mol Med. 2026 Sep 08.

Comprehensive functional testing in fibroblasts has strong utility to diagnose mitochondrial disease.

Johan L K Van Hove, Marisa W Friederich, Roxanne A Van Hove, Jessica C Lee, Kaz M Knight, Tonia E Donovan, Lori Silveira, Rebecca D Ganetzky, Michio Hirano, Jose Abdenur, Merlin G Butler, David Cassiman, Bruce H Cohen, Sarah H Elsea, Gregory M Enns, William A Gahl, Ralitza Gavrilova, Gabrielle C Geddes, Emma E Glamuzina, Amy Goldstein, Richard H Haas, Aneal Khan, Kimberly A Kripps, Austin A Larson, April N Lehman, Uta Lichter-Konecki, Johannes A Mayr, Eva Morava, James T Peterson, Jill A Rosenfeld, Russell P Saneto, Fernando Scaglia, Emily Shelkowitz, Mariella Simon, Joél E G Smet, Wendy E Smith, Claudia Soler-Alfonso, Mark Tarnopolsky, Rudy N A Van Coster, Arnaud V Vanlander, Pieter Vermeersch, Jerry Vockley, Kristen Wigby, Lynne A Wolfe, Saskia B Wortmann, Jennifer H Yang.

Genome sequencing is the first-line diagnostic method for primary mitochondrial diseases (PMDs), yet its effectiveness is limited by variants of uncertain significance or unresolved genetic findings. We systematically evaluated the clinical performance of fibroblast-based functional testing, comprised of respiratory chain enzyme assays, blue native polyacrylamide gel electrophoresis with in-gel activity staining (BN-PAGE), complex I assembly assay, and targeted protein abundance assessments, in a cohort of 204 genetically confirmed PMD patients, 51 healthy controls, and 53 patients with differential diagnoses. Individually, enzyme assays, BN-PAGE, and complex I assembly assay showed sensitivities of 46%, 40%, and 49%, with specificities of 93%, 98%, and 99%, respectively. Combined, the assays achieved an overall sensitivity of 76%, a specificity 93%, a positive predictive value 96%, and a negative predictive value of 67%. Sensitivity was highest for isolated respiratory chain deficiencies, nuclear DNA-encoded mitochondrial translation defects, cofactor deficiencies, and mitochondrial aminoacyl-tRNA synthetase disorders, whereas mitochondrial DNA variants and maintenance defects remained challenging. Secondary mitochondrial dysfunction was rare. The strong clinical utility of comprehensive fibroblast functional testing improves PMD diagnosis when used complementary to genomic sequencing.

DOI: https://doi.org/10.1038/s44321-026-00497-3