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Dynamics of the mammalian pyruvate dehydrogenase complex revealed by in-situ structural analysis.
Nat Commun
January 2025
Center of Cryo-Electron Microscopy, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
The multi-enzyme pyruvate dehydrogenase complex (PDHc) links glycolysis to the citric acid cycle and plays vital roles in metabolism, energy production, and cellular signaling. Although all components have been individually characterized, the intact PDHc structure remains unclear, hampering our understanding of its composition and dynamical catalytic mechanisms. Here, we report the in-situ architecture of intact mammalian PDHc by cryo-electron tomography.
View Article and Find Full Text PDFPKM2-mediated collagen XVII expression is critical for wound repair.
JCI Insight
January 2025
Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Chronic wounds have emerged as a tough clinical challenge. An improved understanding of wound healing mechanisms is paramount. Collagen XVII (COL17), a pivotal constituent of hemidesmosomes, holds considerable promise for regulating epidermal cell adhesion to the basement membrane, as well as for epidermal cell motility and self-renewal of epidermal stem cells.
View Article and Find Full Text PDFThe role of alternative oxidase in the maintenance of cellular redox balance under hypoxia via participation in nitric oxide turnover.
J Exp Bot
January 2025
Morden Research and Development Centre, Agriculture and Agri-Food Canada, Morden, MB, Canada.
Alternative oxidase (AOX) regulates the level of reactive oxygen species and nitric oxide (NO) in plants. While under normoxic conditions it alleviates NO formation, there are several indications that in the conditions of low oxygen such as during seed germination before radicle protrusion, in meristematic stem cells, and in flooded roots AOX can be involved in the production of NO from nitrite. Whereas the first reports considered this role as indirect, more evidence is accumulated that AOX can act as a nitrite: NO reductase.
View Article and Find Full Text PDFItaconate mechanism of action and dissimilation in .
Proc Natl Acad Sci U S A
January 2025
Centre for Tuberculosis Research, Tuberculosis Research Laboratory, Translational Health Science and Technology Institute, National Capital Region Biotech Science Cluster 3rd Milestone, Faridabad, Haryana 121001, India.
Itaconate, an abundant metabolite produced by macrophages upon interferon-γ stimulation, possesses both antibacterial and immunomodulatory properties. Despite its crucial role in immunity and antimicrobial control, its mechanism of action and dissimilation are poorly understood. Here, we demonstrate that infection of mice with increases itaconate levels in lung tissues.
View Article and Find Full Text PDFThe PKM2 activator TEPP-46 suppresses cellular senescence in hydrogen peroxide-induced proximal tubular cells and kidney fibrosis in CD-1 mice.
J Diabetes Investig
January 2025
Faculty of Medicine, Internal Medicine, Shimane University, Izumo, Shimane, Japan.
Aim/introduction: Senescence is a key driver of age-related kidney dysfunction, including diabetic kidney disease. Oxidative stress activates cellular senescence, induces abnormal glycolysis, and is associated with pyruvate kinase muscle isoform 2 (PKM2) dysfunction; however, the mechanisms linking PK activation to cellular senescence have not been elucidated. We hypothesized that PKM2 activation by TEPP-46 could suppress oxidative stress-induced renal tubular cell injury and cellular senescence.
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