PNPO-PLP Axis Senses Prolonged Hypoxia by Regulating Lysosomal Activity
Sekine, H.; Takeda, H.; Kishino, A.; Anzawa, H.; Isagawa, T.; Ota, N.; Kato, N.; Kimura, S.; Liu, Z.; Kato, K.; Katsuoka, F.; Yamamoto, M.; Miura, F.; Ito, T.; Takahashi, M.; Izumi, Y.; Fujita, H.; Yamagata, H.; Takeda, N.; Bamba, T.; Suzuki, N.; Kinoshita, K.; Motohashi, H.
Show abstract
Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen sensing systems inducing acute hypoxic response, including HIF pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here, we show that pyridoxine 5-phosphate oxidase (PNPO) that catalyzes bioactivation of vitamin B6 serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decline of PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5-phosphate (PLP), and inhibited lysosomal activity, leading to the augmentation of inflammatory response of macrophages. The PNPO-PLP axis creates a distinct layer of oxygen sensing, which gradually turns down and up the PLP-dependent metabolism according to prolonged changes in oxygen availability.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Cellular Stress Signaling Activates Type-I IFN Response Through FOXO3-regulated Lamin Posttranslational Modification 97%
- Mechanisms of Epigenomic and Functional Convergence Between Glucocorticoid and IL4-Driven Macrophage Programming 96%
- Mitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity 96%
Similar papers in this journal
- Novel adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments 97%
- Electron transport inhibition increases cellular dependence on purine transport and salvage 95%
- A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion 94%
Similar papers in this journal
- Folate depletion induces erythroid differentiation through perturbation of de novo purine synthesis 97%
- Type I interferon potentiates metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice 95%
- Modulating immune cell fate and inflammation through CRISPR-mediated DNA methylation editing 95%
Similar papers in this journal
- Mitochondrial complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathology 95%
- Hexokinase detachment from mitochondria drives the Warburg effect to support compartmentalized ATP production 95%
- Weak neuronal glycolysis sustains cognition and organismal fitness 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.