bims-cytox1 2025-09-28 papers

Genes (Basel). 2025 Sep 11. pii: 1069. [Epub ahead of print]16(9):

Mitochondrial Complex IV Deficiency Nuclear Type 11 Caused by a Novel Start-Lost Variant in the COX20 Gene.

Anna Kuchina, Artem Borovikov, Olga Sidorova, Maria Orlova, Oxana Ryzhkova, Igor Zaigrin, Aysylu Murtazina.

Background: The COX20 gene encodes a critical assembly factor for cytochrome C oxidase (complex IV), and biallelic loss-of-function variants in this gene cause mitochondrial complex IV deficiency, typically presenting in infancy or childhood with hypotonia, ataxia, neuropathy, or dystonia. Methods: This study describes an adult male patient with a broad clinical spectrum of central and peripheral nervous system involvement. Different medical genetic tests were performed for the patient, and only whole-genome trio sequencing identified pathogenic variants in the COX20 gene. A review of previously reported cases was conducted to compare clinical and imaging findings. Results: Two compound heterozygous COX20 variants in were identified: a known missense variant (c.41A>G; p.Lys14Arg) disrupting splicing, and a novel start-loss variant (c.2T>C; p.Met1?). The patient exhibited progressive ataxia, pyramidal signs, and peripheral neuropathy, accompanied by cervical spinal cord atrophy on spinal cord MRI and lower leg muscle fat infiltration on muscle MRI, an imaging feature not previously emphasized in COX20-related disease. Conclusions: A review of previously reported cases underscores broad clinical variability of the COX20-associated disorder, which may contribute to a prolonged diagnostic odyssey.

Keywords: COX20; ataxia; mitochondrial complex IV deficiency; neuropathy

DOI: https://doi.org/10.3390/genes16091069

Biomolecules. 2025 Aug 22. pii: 1209. [Epub ahead of print]15(9):

Supercomplex Restructuring in Heart Mitochondria of COX7A1-Deficient Mice.

Lauren Pavelich, Lucynda Pham, Paul Stemmer, Icksoo Lee, Lawrence I Grossman, Maik Hüttemann, Tasnim Arroum.

The role of electron transport chain supercomplexes and factors that regulate their composition in a tissue- and species-specific manner are not fully understood. Tissue-specific isoforms have been reported for cytochrome c oxidase (COX), which may contribute to such regulation. Therefore, we here investigated COX activity and structural organization in wild-type (WT) and COX7A1 knockout (KO) mice, which lack the heart/skeletal muscle isoform of COX subunit VIIa. COX7A1 KO mice showed a 30% reduction in total COX activity in the heart. Although the activity of COX in the monomers and I+III2+IVn supercomplexes (SCs) remained unchanged, a marked reduction in COX dimers and unknown COX-containing species IVx and IVy contributed to the overall reduction in COX activity. Furthermore, we observed that COX7A2 substituted for COX7A1 in COX monomers, dimers, and all COX-containing SCs in the KO mice, indicating a compensatory mechanism to preserve COX functionality. Collectively, these results suggest that COX7A1 plays an important role in maintaining structural stability; however, they also suggest that loss of COX7A1 is compensated by its replacement with COX7A2.

Keywords: COX7aH; COX7aL; cytochrome c oxidase; heart; isoforms

DOI: https://doi.org/10.3390/biom15091209

Int J Biol Macromol. 2025 Sep 19. pii: S0141-8130(25)08288-1. [Epub ahead of print] 147731

Genome-wide identification of cytochrome c oxidase genes in cotton and functional characterization of GhCOX11 in drought and cold stress.

Chenhui Li, Xingzhi Wei, Qihua Chen, Xinyue Xu, Weijiang Tian, Xiumei Dai, Xiaofeng Su, Wenfang Guo, Hongmei Cheng, Huan Si, Peilin Wang, Huiming Guo.

Abiotic stresses significantly impair crop morphogenesis, physiological function, metabolic networks, and yield. Moreover, multiple stress factors often act synergistically, highlighting the urgent need to breed multi-stress-tolerant, high-quality cotton varieties. In this study, the cytochrome C oxidase (COX) gene family was identified genome-wide in Gossypium hirsutum using a Hidden Markov Model (HMM), revealing 50 members categorized into 12 subfamilies. Chromosomal mapping revealed an uneven distribution across 22 chromosomes, with evidence of both intra- and interspecific collinearity. Further functional analysis focused on GhCOX11, which was broadly expressed across tissues and significantly upregulated under drought, salt, and low-temperature stresses. Silencing GhCOX11 led to increased leaf wilting, reduced relative water content, and elevated hydrogen peroxide (H2O2) accumulation under drought stress. Conversely, overexpressing GhCOX11 in tobacco significantly enhanced drought and cold tolerance, as evidenced by improved root development and increased antioxidant enzyme activity. The transcription factor DREB1D was found to specifically bind the low-temperature response element (LTR) in the GhCOX11 promoter, activating its expression. Additionally, GhCOX11 interacted with members of the glutathione peroxidase (GPX) family to synergistically scavenge reactive oxygen species (ROS), thereby maintaining cellular redox homeostasis. These findings clarify the role of GhCOX11 in plant stress responses through ROS regulation and offer promising gene candidates for improving crop stress resilience.

Keywords: Cotton; Genome-wide identification; GhCOX11; Glutathione peroxidase (GPX); Reactive oxygen species (ROS)

DOI: https://doi.org/10.1016/j.ijbiomac.2025.147731