bims-cytox1 2025-03-02 papers

Case Rep Med. 2025 ;2025 1823517

A Case of Infantile Reversible Cytochrome C Oxidase Deficiency Myopathy in Taiwan: A 4-Year Follow-Up.

Yu-Ting Ma, Ju-Li Lin, Ming-Wei Lai, I-Jun Chou, Mao-Sheng Hwang.

Infantile reversible cytochrome c oxidase (COX) deficiency myopathy is a mitochondrial rare disease with onset age of first day to three months with symptoms of generalized muscle weakness and severe hypotonia. Despite its initial serious conditions, the symptoms may improve spontaneously later in their life, with the so-called "benign" myopathy accordingly. This benign mitochondrial myopathy might be improved in their later life, which is different from most mitochondrial myopathies with progression by age. Therefore, we depicted the rare case of her clinical course during our medical practice, anticipating to provide more information of this rare disease.

Keywords: benign COX deficiency myopathy; cytochrome C oxidase; mitochondria

DOI: https://doi.org/10.1155/carm/1823517

Antioxidants (Basel). 2025 Jan 24. pii: 142. [Epub ahead of print]14(2):

Copper-Induced Enhancement of Glioblastoma Tumorigenicity via Cytochrome C Oxidase.

Claudia R Oliva, Md Yousuf Ali, Susanne Flor, Corinne E Griguer.

Copper is an essential trace element, yet chronic copper exposure can lead to toxicity in humans, and high levels of copper have been found in the blood or tumors of patients with various forms of cancer and may affect cancer severity and response to treatment. Copper is required for the activation of cytochrome c oxidase (CcO), the mitochondrial complex that facilitates oxidative phosphorylation (OXPHOS)-mediated ATP production. We recently reported that the increased activation of CcO underlies the acquisition of treatment resistance in glioblastoma (GBM) cells. However, the potential role of copper in GBM progression or treatment resistance has not been investigated. Here, we present evidence that exposure to 20 µM copper, the maximum allowable limit for public water supplies set by the U.S. Environmental Protection Agency, promotes GBM tumor growth and reduces overall survival in vivo and increases GBM cell resistance to radiation and chemotherapy in vitro. In vitro exposure to 20 µM copper substantially increased the activity of CcO, elevated the rate and level of ATP production, and triggered a metabolic shift to an OXPHOS phenotype in GBM cells. Furthermore, copper exposure led to a substantial increase in the accumulation of glutathione and glutathione precursors in these cells. These findings establish copper as a tumor promoter in GBM and suggest that copper mediates these effects through the upregulation of CcO activity, which enhances OXPHOS metabolism and glutathione production.

Keywords: copper; cytochrome c oxidase; glioblastoma; oxphos

DOI: https://doi.org/10.3390/antiox14020142

Antioxidants (Basel). 2025 Feb 12. pii: 211. [Epub ahead of print]14(2):

Protein Nitration in Patients with Mitochondrial Diseases.

Jomênica B Livramento, Gabriela S Rodrigues, Jean Faber, Luis A de Souza Filho, Felipo V Moura, Camila D S Barros, Wladimir B V R Pinto, Beny Schmidt, Acary S B Oliveira, Beatriz H Kiyomoto, Célia H Tengan.

Mitochondrial diseases are complex disorders caused by nuclear or mitochondrial DNA mutations, leading to oxidative phosphorylation deficiency and excessive production of reactive oxygen species (ROS). While ROS have been well established in the pathogenesis of these diseases, the role of reactive nitrogen species (RNS) remains unclear. In this study, we performed a quantitative analysis of muscle fibers to investigate the relationship between protein nitration and mitochondrial abnormalities (mitochondrial proliferation and cytochrome-c oxidase (COX) deficiency) and factors like genotype, muscle damage, and age. A total of 1961 muscle fibers (303 from 4 controls and 1658 from 29 patients with mitochondrial diseases) were analyzed by immunostaining for nitro-tyrosine. Contrary to previous findings, which identified nitro-tyrosine only in small muscle vessels, we observed a broader distribution affecting the sarcolemma and sarcoplasm. Using multivariate techniques, we identified a significant correlation between protein nitration and mitochondrial proliferation but found no associations with COX deficiency, age, muscle damage, or genotype. These findings suggest that nitrative stress may contribute to mitochondrial dysfunction or play a role in signaling processes that induce mitochondrial biogenesis. Our results provide new insights into the molecular mechanisms of mitochondrial diseases and highlight the potential relevance of protein nitration.

Keywords: mitochondrial DNA (mtDNA); mitochondrial diseases; nitrative stress; nitric oxide; oxidative stress; protein nitration; reactive nitrogen species (RNS); reactive oxygen species (ROS)

DOI: https://doi.org/10.3390/antiox14020211