![]() ![]() SURF1 protein is located in the mitochondrial inner membrane and is involved in the assembly of CIV, i.e., the cytochrome c oxidase (COX) (Fig. SURF1 gene contains 9 exons, is located on chromosome 9q34, and encodes a protein that is highly conserved among eukaryotes and prokaryotes 10. One of the most frequently mutated nuclear genes in LS is the SURF1 gene (Surfeit locus protein 1, NM_003172.2) 7, 8, 9. The most commonly affected mitochondrial complexes in LS are complex I (CI) and complex IV (CIV) 6. Mutations in more than 75 genes of nuclear or mitochondrial DNA (mtDNA) can cause LS 5. Leigh syndrome (LS) affects 1 in 36,000 newborns 3 and causes lactic acidosis and symmetric lesions in the central nervous system (CNS), predominantly of basal ganglia and brainstem, leading to intellectual disability and muscle weakness with a peak of mortality before three years of age 4. The most severe pediatric manifestation of mitochondrial disease is Leigh syndrome (OMIM #256000) 2. Mitochondrial disease represents the largest class of inborn errors of metabolism mainly comprising monogenic disorders that disrupt oxidative phosphorylation (OXPHOS) 1. Our findings provide mechanistic insights and suggest potential interventional strategies for a rare mitochondrial disease. SURF1 gene augmentation and PGC1A induction via bezafibrate treatment supported the metabolic programming of LS NPCs, leading to restored neuronal morphogenesis. ![]() LS NPCs carrying mutations in the complex I gene NDUFS4 recapitulated morphogenesis defects. The defects emerged at the level of neural progenitor cells (NPCs), which retained a glycolytic proliferative state that failed to instruct neuronal morphogenesis. Single-cell RNA-sequencing and multi-omics analysis revealed compromised neuronal morphogenesis in mutant neural cultures and brain organoids. ![]() Using patient-derived induced pluripotent stem cells and CRISPR/Cas9 engineering, we developed a human model of LS caused by mutations in the complex IV assembly gene SURF1. The lack of effective models hampers our understanding of the mechanisms underlying the neuronal pathology of LS. Leigh syndrome (LS) is a severe manifestation of mitochondrial disease in children and is currently incurable. ![]() Nature Communications volume 12, Article number: 1929 ( 2021) While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.Ĭancer fucosylation and personalized medicine glycan glycan alteration glycoprotein glycosylation sialylation tumor.Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome Therefore, studying glycans holds great potential for better diagnostic markers as well as developing more efficient treatment strategies in human cancers. Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations. Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy. In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations. Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans. Cancer as the leading cause of death worldwide has many issues that still need to be addressed. ![]()
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |