Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis
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Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis
Fatty acid β-oxidation (FAO) is the main bioenergy pathways in human prostate cancer (PCa) and promising new therapies vulnerabilities. Here we demonstrate the therapeutic efficacy of targeting FAO in prostate tumor clinical cultured ex vivo, and identify DECR1, encoding the enzyme rate-limiting for the acid oxidation of polyunsaturated fats (PUFAs), as excited expressed in tissues of PCa and was associated with survival of relapse-free over short. DECR1 is androgen receptor (AR) gene targets of negative-regulated and, therefore, can promote PCa cell survival and resistance to therapy targeting AR.
DECR1 knockdown selectively inhibit β-oxidation of PUFAs, inhibits the proliferation and migration of PCa cells, including treatment-resistant line, and suppressed tumor cell proliferation and metastasis in xenograft mouse models. Mechanical, caused DECR1 targeting cellular accumulation of PUFA, enhanced mitochondrial oxidative stress and lipid peroxidation, and induced ferroptosis. These findings involves the oxidation of PUFAs through DECR1 as unexplored aspects of FAO that promotes PCa cell survival.
Reactive oxygen species (ROS) and mitochondria play an important role in regulating platelet function. determining platelet activation drastic changes in redox balance and the metabolism of platelets. Indeed, several signaling pathways have been shown to induce ROS production by NAPDH oxidase (NOX) and mitochondria, after activation of platelets. Platelet-derived ROS, in turn, further increases ROS production and consequent platelet activation, adhesion and recruitment in the loop auto-reinforcing.
This vicious circle results in platelet procoagulant phenotype and apoptosis, both accounting high thrombotic risk in oxidative stress-related illnesses. This review seeks to explain the molecular mechanisms underlying the production of ROS during platelet activation and altered redox balance effect on platelet function, with a focus on the major progress that has been made in redox biology of platelets. Furthermore, given the increased interest in this field, we also describe a method of up-to-date to detect platelets, ROS and bioenergy profile platelets, which have been proposed as potential biomarkers of disease.
Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis
Both aerobic glycolysis and mitochondrial respiration necessary for osteoclast differentiation
Excessive bone resorption over bone formation is the root cause of bone loss that leads to osteoporosis fractures. Development of new antiresorptive therapy calls for a holistic understanding of osteoclast differentiation and function.
Although much has been learned about the regulation of the molecular biology of osteoclasts, little is known about the metabolism and bioenergetics requirements during osteoclastogenesis. Here, we report that glucose metabolism through oxidative phosphorylation (OXPHOS) is the dominant bioenergy pathways to support osteoclast differentiation. Meanwhile, increased production of lactate from glucose, which is known as aerobic glycolysis when oxygen is plentiful, it is also important for osteoclastogenesis.
Genetic deletion in osteoclast progenitor Glut1 reduce aerobic glycolysis without sacrificing OXPHOS, but nonetheless reduced osteoclast differentiation in vitro. The progenitor Glut1 deficiency leads to osteopetrosis because fewer osteoclasts specialized in female rats. Thus, Glut1-mediated glucose metabolism through the production of lactic and OXPHOS both required for normal osteoclastogenesis.
