bims-cytox1 2024-12-01 papers

Biochim Biophys Acta Mol Basis Dis. 2024 Nov 27. pii: S0925-4439(24)00561-1. [Epub ahead of print] 167567

Tissue-specific adaptations to cytochrome c oxidase deficiency shape physiological outcomes.

Milica Popovic, Lea Isermann, Simon Geißen, Katharina Senft, Theodoros Georgomanolis, Stephan Baldus, Christian Frezza, Aleksandra Trifunovic.

It becomes increasingly clear that the tissue specificity of mitochondrial diseases might in part rely on their ability to compensate for mitochondrial defects, contributing to the heterogeneous nature of mitochondrial diseases. Here, we investigated tissue-specific responses to cytochrome c oxidase (CIV or COX) deficiency using a mouse model with heart and skeletal muscle-specific depletion of the COX assembly factor COX10. At three weeks of age, both tissues exhibit pronounced CIV depletion but respond differently to oxidative phosphorylation (OXPHOS) impairment. Heart-specific COX10 depletion caused severe dilated cardiomyopathy, while skeletal muscle experiences less damage. Cardiac CIV deficiency triggered extensive metabolic remodelling and stress response activation, potentially worsening cardiomyopathy, whereas skeletal muscle showed no stress response or significant metabolic changes. Our findings highlight distinct tissue capacities for managing CIV deficiency, explaining how identical primary defects can lead to different phenotypic outcomes and contribute to the heterogeneous progression of mitochondrial diseases.

DOI: https://doi.org/10.1016/j.bbadis.2024.167567

J Cell Mol Med. 2024 Nov;28(22): e70234

Abnormal Expression of COX5B Gene and Disorder of Mitochondrial Function in Cryptorchid Rats.

Xuehan Wang, Dashuai Miao, Songyi Ye, Hua Xian, Wenliang Ge.

Cryptorchidism is one of the most common congenital malformations in the paediatric genitourinary tract. Data analysis of cryptorchidism-related datasets in the GEO database and gene sequencing results from our institution, along with bioinformatic analysis of the merged mitochondrial gene datasets, revealed that COX5B is differentially expressed in the testes of children with cryptorchidism. Its encoded protein has attracted our attention as a key component of the mitochondrial respiratory chain complex IV. This study aims to explore the COX5B gene expression changes and related mitochondrial issues in cryptorchid rats. For this purpose, we established a cryptorchid rat model by surgery and used molecular biology and biochemistry techniques to detect and analyse the expression level of the COX5B gene and mitochondrial function indexes. The results indicated a significant decrease in COX5B gene expression in the affected testis of cryptorchid rats. The knockdown of COX5B expression in TM3 cells could be observed as the aggravation of cellular senescence, which led to the reduction of proliferation, as well as accompanied by the obvious disorders of mitochondrial function, including the increase of ROS and the decrease of ATP, in which MMP was significantly reduced. This suggests that the COX5B gene may play an important role in cryptorchid testis-induced reproductive system damage and may be a new target for small molecule-targeted therapy.

Keywords: COX5B gene; TM3 cell; cryptorchidism; mitochondrial function

DOI: https://doi.org/10.1111/jcmm.70234

Mol Biol Rep. 2024 Nov 26. 52(1): 17

Characterisation of cytochrome c oxidase-coding genes from mung bean and their response to cadmium stress based on genome-wide identification and transcriptome analysis.

Yan Leng, Zhuan-Bin Niu, Shao-Hua Liu, Fu-Jun Qiao, Gui-Fang Liu, Bin Cheng, Shi-Weng Li.

BACKGROUND: Cytochrome c oxidase (COX) is a crucial mitochondrial enzyme in the electron transport chain of plants, implicated in energy production and stress responses. Despite its importance, the function of COX in leguminous plants, especially under heavy metal stress like cadmium (Cd), remains understudied.
METHODS AND RESULTS: In this study, COX genes (COX s) were identified based on the genome annotation file in mung bean (Vigna radiata (Linn.) R. Wilczek), and the gene structure, physicochemical properties and systematic relationships of the relevant amino acid sequences were analyzed by using bioinformatics method. The effects of Cd on the transcription levels and activities of COX in mung bean roots, stems, and leaves were detected to understand the mechanism of COX in mung bean in response to cadmium (Cd) stress. Transcriptome sequencing revealed tissue-specific expression with roots showed the highest levels. Cd stress significantly altered the expression and activity of VrCOXs, particularly in roots and stems, with varied responses among different genes.
CONCLUSIONS: The differential response of VrCOX s to Cd stress indicates a role in the plant stress tolerance mechanism. The study provides insights into the function of COXs in legumes and a foundation for further research into Cd tolerance mechanisms, which could be vital for enhancing legume production and ensuring food safety in contaminated environments.

Keywords: Cadmium (Cd) stress; Cytochrome c oxidase; Mung bean; Transcriptome

DOI: https://doi.org/10.1007/s11033-024-10102-w