bims-cytox1 2025-11-30 papers

Plant Physiol Biochem. 2025 Nov 05. pii: S0981-9428(25)01271-9. [Epub ahead of print]230 110743

HIGD2 confers hypoxic stress tolerance in rice by improving mitochondrial function.

Flooding and oxygen deprivation severely impair mitochondrial energy metabolism in rice, reducing growth and survival under waterlogged conditions. To elucidate the mechanisms of mitochondrial adaptation during hypoxia, we characterized OsHIGD2, a rice gene encoding a hypoxia-induced gene domain (HIGD) protein. Transgenic rice lines overexpressing OsHIGD2 and CRISPR/Cas9 knockout mutants were generated to investigate its functional role under low-oxygen stress. The expression of OsHIGD2 was strongly induced by submergence and hypoxia, particularly during the early stress phase. Overexpression lines exhibited markedly improved survival and recovery after 7 days of hypoxic treatment, showing two-to threefold increases in leaf number, length, and area compared with wild-type controls. Conversely, knockout mutants displayed growth retardation and enhanced electrolyte leakage, indicating greater cellular damage. Overexpression lines maintained significantly higher cytochrome c oxidase (complex IV) activity under hypoxia, whereas mutants showed decreased activity, suggesting that OsHIGD2 contributes to sustaining mitochondrial respiration during oxygen limitation. No significant differences in NAD+ content were observed among the lines, implying that OsHIGD2-mediated tolerance mainly involves preservation of mitochondrial integrity rather than glycolytic adjustment. Collectively, these results demonstrate that OsHIGD2 enhances hypoxia tolerance in rice by maintaining mitochondrial function and respiratory efficiency, offering insights into mitochondrial regulation of flood resilience in crops.

Keywords: Cytochrome c oxidase; Energy metabolism; HIGD2; Hypoxia; Mitochondria; Rice; Submergence

DOI: https://doi.org/10.1016/j.plaphy.2025.110743

Curr Issues Mol Biol. 2025 Oct 29. pii: 901. [Epub ahead of print]47(11):

Novel Variants in Sperm Mitochondrial Cytochrome C Oxidase II (MT-CO2) Gene Associated with Asthenozoospermia in Jordan.

Mazhar Salim Al Zoubi, Razan N AlQuraan, Asmaa Al-Smadi, Mohammad A AlSmadi, Manal AbuAlArja, Almuthanna K Alkaraki, Bahaa Al-Trad, Raed M Al-Zoubi, Khalid Al-Batayneh.

BACKGROUND: Asthenozoospermia is defined as a condition in which the total motility of sperm in a semen sample is less than 40%. Due to impairing sperm motility, asthenozoospermia was linked to different mitochondrial DNA (mtDNA) alterations. The current study aimed to investigate the relationship between MT-CO2 gene variants and the development of asthenozoospermia and male infertility in the Jordanian population.
MATERIALS AND METHODS: Semen samples were collected from 196 men, including 119 asthenozoospermic (infertile) and 77 normozoospermia (control), from the Royal Jordanian Medical Services in vitro fertilization (IVF) unit. The isolated mitochondrial DNA (mtDNA) was subjected to a polymerase chain reaction to amplify the MT-CO2 gene. Genetic variants were screened using direct Sanger sequencing. Genotypes and allele frequencies between the case and control groups were compared by the chi-square test and Fisher's exact test.
RESULTS: Three novel variants in the MT-CO2 gene were identified in nine asthenozoospermic cases, including two missense variants (m.8222T>A and m.7997G>A) and one synonymous variant (m.7846 A>G). In addition, the current study reported twenty-three known substitutions. In particular, the rs1556423316 T>C variant showed a significant association with asthenozoospermic infertile men in the studied population (p < 0.05).
CONCLUSION: The detected missense variants in the MT-CO2 gene in asthenozoospermic infertile men underscore the important role of these variants in the development of asthenozoospermic male infertility.

Keywords: MT-CO2; asthenozoospermia; male infertility; mtDNA

DOI: https://doi.org/10.3390/cimb47110901

Acta Pharm Sin B. 2025 Nov;15(11): 5832-5853

High glucose induces hippocampal neuron impairment through the SKP1/COX7C pathway: A potential mechanism for perimenopausal depression.

Ziqi Wang, Zhiyuan Liu, Sijia Feng, Xintong Song, Dequan Liu, Ning Ma, Xinyue Zhang, Weiwei Liu, Dan Ohtan Wang, Xiaoling Liu, Takashi Ikejima.

Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCDSS) and the VCD depression resilient group (VCDRES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.

Keywords: COX7C; Depression; Glucose; Mitochondrion; Neuron; Perimenopause; SKP1; Ubiquitination

DOI: https://doi.org/10.1016/j.apsb.2025.09.003