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Mitochondrial diseases are inherited disorders that impede the mitochondria's ability to produce sufficient energy for the cells. They can affect different parts of the body, notably the brain. Neurological symptoms and epilepsy are prevalent in patients with mitochondrial disorders. The epileptogenicity of mitochondrial disorder is a complex process involving the intricate interplay between abnormal energy metabolism and neuronal activity. Several modalities have been used to detect seizures in different disorders including mitochondrial disorders. EEG serve as the gold standard for diagnosis and localization, commonly complemented by additional imaging modalities to enhance source localization. In the current work, we propose the use of functional near-infrared spectroscopy (fNIRS) to identify the occurrence of epilepsy and seizure in patients with mitochondrial disorders. fNIRS proves an advantageous imaging technique due to its portability and insensitivity to motion especially for imaging infants and children. It has added a valuable factor to our understanding of energy metabolism and neuronal activity. Its real-time monitoring with high spatial resolution supplements traditional diagnostic tools such as EEG and provides a comprehensive understanding of seizure and epileptogenesis. The utility of fNIRS extends to its ability to detect changes in Cytochrome c oxidase (CcO) which is a crucial enzyme in cellular respiration. This facet enhances our insight into the metabolic dimension of epilepsy related to mitochondrial dysfunction. By providing valuable insights into both energy metabolism and neuronal activity, fNIRS emerges as a promising imaging technique for unveiling the complexities of mitochondrial disorders and their neurological manifestations.
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http://dx.doi.org/10.1016/j.neurot.2024.e00323 | DOI Listing |
Proc Natl Acad Sci U S A
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug De
Proliferative retinopathy is a leading cause of irreversible blindness in humans; however, the molecular mechanisms behind the immune cell-mediated retinal angiogenesis remain poorly elucidated. Here, using single-cell RNA sequencing in an oxygen-induced retinopathy (OIR) model, we identified an enrichment of sorting nexin (SNX)-related pathways, with SNX3, a member of the SNX family that is involved in endosomal sorting and trafficking, being significantly upregulated in the myeloid cell subpopulations of OIR retinas. Immunostaining showed that SNX3 expression is markedly increased in the retinal microglia/macrophages of mice with OIR, which is mainly located within and around the neovascular tufts.
View Article and Find Full Text PDFMetabolomics
September 2025
Laboratoire de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire, Angers, France.
Introduction: The definition of Leber's hereditary optic neuropathy (LHON) does not take into account a preclinical phase during which the thickness of retinal nerve fiber layer (RNFL) is increased, prior to optic nerve atrophy, reducing the chances of visual recovery.
Objectives: Search for a metabolomic signature characterizing this preclinical phase and identify biomarkers predicting the risk of LHON onset.
Methods And Results: The blood and tear metabolomic profiles of 90 asymptomatic LHON mutation carriers followed for one year will be explored as a function of RNFL thickness and compared to those of a healthy control.
Hum Genet
September 2025
College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, 28 Fuxing Road, Beijing, 100853, China.
Recessive variants in TWNK cause syndromes arising from mitochondrial DNA (mtDNA) depletion. Hearing loss is the most prevalent manifestation in individuals with these disorders. However, the clinical and pathophysiological features have not been fully elucidated.
View Article and Find Full Text PDFMol Biomed
September 2025
National Key Laboratory of Immunity and Inflammation & Institute of Immunology, College of Basic Medical Sciences, Naval Medical University, Shanghai, 200433, China.
Dendritic cells (DCs) play a central role in coordinating immune responses by linking innate and adaptive immunity through their exceptional antigen-presenting capabilities. Recent studies reveal that metabolic reprogramming-especially pathways involving acetyl-coenzyme A (acetyl-CoA)-critically influences DC function in both physiological and pathological contexts. This review consolidates current knowledge on how environmental factors, tumor-derived signals, and intrinsic metabolic pathways collectively regulate DC development, subset differentiation, and functional adaptability.
View Article and Find Full Text PDFFASEB J
September 2025
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials
The onset and progression of periodontitis are closely related to metabolic reprogramming in the periodontal microenvironment, with osteoclasts playing a critical role in tissue destruction. Single-cell RNA sequencing (scRNA-seq) of periodontal tissues from healthy individuals and patients with severe chronic periodontitis revealed a significant increase in the expression of mitochondrial-related genes during osteoclast differentiation, suggesting the critical role of mitochondrial function in this process. This study investigates the potential of the novel mitoribosome-targeting antibiotic radezolid in inhibiting osteoclast differentiation.
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