PER1 interaction with GPX1 regulates metabolic homeostasis under oxidative stress

Abstract

Metabolism serves mammalian feeding and active behavior, and is controlled by circadian clock. The molecular mechanism by which clock factors regulate metabolic homeostasis under oxidative stress is unclear. Here, we have characterized that the daily oxygen consumption rhythm was deregulated in Per1 deficient mice. Per1 deficiency impaired daily mitochondrial dynamics and deregulated cellular GPx-related ROS fluctuations in the peripheral organs. We identified that PER1 enhanced GPx activity through PER1/GPX1 interaction in cytoplasm, consequently improving the oxidative phosphorylation efficiency of mitochondria. Per1 expression was specifically elevated in the fasting peripheral organs for protecting mitochondrial from oxidation stress. These observations reveal that Per1 -driven mitochondrial dynamics is a critical effector mechanism for the regulation of mitochondrial function in response to oxidation stress.

Expression of circadian clock genes in leukocytes of patients with Meniere's disease

“…35 As a result, the effect of possible MD triggers on the circadian clock could be obviously revealed in PER1 expression. Notably, the lack of PER1 deregulated cellular glutathione peroxidase-related reactive oxygen species fluctuations, 54 and may augment the oxidative stress in the hair cells. This may account for our results showing that the lower expression of PER1 was associated with higher PTA of the affected in patients with MD.…”

PER1 Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Ovarian Cancer

“…From a non-tumor perspective, PER1 is related to conditions such as Parkinson's disease, obesity, sleep, drug resistance, and premature ovarian insufficiency (Zheng et al, 2019;Delgado-Lara et al, 2020;EmeklI et al, 2020;Mabrouk et al, 2020;Arellanes-Licea et al, 2021). PER1 enhances the activity of GPX through the interaction of PER1 and GPX1 in the cytoplasm, thereby improving the oxidative phosphorylation efficiency of mitochondria (Sun et al, 2020). Current studies indicate that the clock gene PER1 is downregulated in a variety of tumors and plays an important part in promoting tumor progression.…”

“…Its main functions involve regulating the body's circadian rhythm, regulating the cell cycle, and promoting DNA damage repair. Many studies have shown that PER1 directly regulates levels of reactive oxygen species in multiple organs and regulates key effectors of energy substrate utilization in response to daily behavioral rhythms and oxidative stress, thereby maintaining the daily rhythms of mitochondrial morphology and function (Sun et al, 2020). Changes in expression levels of PER1 have been found in some cancers, including pancreatic cancer (Guo et al, 2020), oral squamous cell carcinoma (Yang et al, 2020), endometrial cancer (Wang et al, 2020), colorectal cancer (Holipah and Kuroda, 2020), and non-small-cell carcinoma (Lin et al, 2020), but this has not been studied in OV.…”

Selenoprotein GPX1 is a prognostic and chemotherapy-related biomarker for brain lower grade glioma

“…The antioxidant enzyme GPX1, was the rst discovered mammalian selenoprotein in GPXs, which is commonly found in cell mitochondria and cytoplasm, has been linked to tumor spread and transformation in tumor cells [13,14]. High oxidative stress response rates have been linked to a variety of chronic diseases, including cancer, arteriosclerosis, chronic in ammatory process, and neurodegeneration [15]. GPX1 was discovered to protect cortical neurons from exogenous oxidative stress-inducing chemicals, preventing oxidative insults to the brain [10].…”