A “short-cut” response of autophagy to oxidative stress: oxygen-dependent activity of a lysine demethylase guides the activity of ULK1 during hypoxia

Yu, Ge; Klionsky, Daniel J.

doi:10.1080/15548627.2022.2089957

Cited by 7 publications

(4 citation statements)

References 7 publications

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“…Leucine plays an important role in the synthesis of skeletal muscle proteins. Lysine can neutralize free-radical electrons generated during the oxidation of unsaturated fatty acids and is an important raw material for nerve cells and hemoglobin synthesis, which can effectively improve the body’s hypoxic and central fatigue states [ 21 ]. Whey protein is mainly composed of lactalbumins and lactoglobulins, which have various physiological activities.…”

Section: Discussionmentioning

confidence: 99%

“…POPs are also rich in lysine, aspartic acid, and glutamic acid [ 20 ]. Lysine acts as an electron acceptor to neutralize free-radical electrons generated during the oxidation of unsaturated fatty acids, while aspartic and glutamic acids can chelate metal ions and inhibit the occurrence of oxidative stress [ 21 ]. POPs also present potential hypotensive activity, and peptide bonds consisting of hydrophobic amino acids are preferentially hydrolyzed during the enzymatic preparation of peanut peptides, resulting in a higher content of hydrophobic amino residues in peanut peptides, thus possessing better angiotensin-converting enzyme-inhibitory activity [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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The Effects of Peanut Oligopeptides on Exercise-Induced Fatigue in Mice and Its Underlying Mechanism

Liu

et al. 2023

Nutrients

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The aim of this study was to clarify the anti-fatigue effect of peanut oligopeptides (POPs) in mice and to investigate its possible underlying mechanism. A total of 150 male ICR mice were randomly assigned into five groups: control, whey protein (0.50 g/kg·bw), and three peanut peptide groups (0.25, 0.50, and 1.00 g/kg·bw). All the mice were treated with intra-gastric administration for 30 days. Following the intervention, a weight-loaded swimming test, blood lactate concentration, glycogen content, the activities of antioxidant factors and energy metabolism enzymes, and the function of mitochondria in the skeletal muscle were examined. The results show that POP intervention significantly prolonged the exhaustive swimming time, decreased blood lactate concentration levels, regulated the process of energy metabolism, and increased the level of antioxidant enzymes, muscle glycogen, and expressions of mtTFA and NRF-1 in the mitochondria of the gastrocnemius muscle. The results suggest that POPs produce an anti-fatigue effect in the animals, and they may exert this effect through the mechanism of improving the animals’ antioxidant capacity to reduce oxidative damage levels and regulating the process of energy metabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Effects of Peanut Oligopeptides on Exercise-Induced Fatigue in Mice and Its Underlying Mechanism

Liu

et al. 2023

Nutrients

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“…Similarly, the systemic deletion of ATG7 restricts the growth of tumor xenografts with arginine deficiency, which reflects the decrease of arginine level in circulation, which is caused by the enhancement of arginine-releasing enzyme 1 (ARG1) released by autophagy-deficient hepatocytes [ 174 ]. The beclin1 gene was found in human hepatocellular carcinoma, breast cancer, ovarian cancer, and prostate cancer cells, which is an essential gene in the autophagy process [ 93 , [178] , [179] , [180] ]. In Beclin 1 ± mouse model, the spontaneous rate of tumor cells is high [ 181 , 182 ], which indicates that autophagy is a tumor inhibition mechanism [ 57 , 145 , 179 , 183 ].…”

Section: Ferroptosis Autophagy and Tumorsmentioning

confidence: 99%

Ferroptosis, autophagy, tumor and immunity

Xie,

Zhou,

Wang

et al. 2023

Heliyon

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“…Intermittent fasting regimens involving alternate day fasting or time-restricted feeding for several days have had beneficial effects in obesity, diabetes, and NASH [49][50][51]. Moreover, these beneficial effects induced by fasting have been associated with activation of autophagy [16,49,[52][53][54][55]. Esrra protein is induced by fasting/starvation (Figure 6A) [48]; and, it is noteworthy that hepatic Esrra overexpression in mice fed WDF activated the Esrra-Rplp1-lysosome pathway, improved autophagy, and reduced hepatosteatosis, inflammation, and fibrosis compared to null mice when both were fed WDF (Figure 5A-H).…”

Section: Alternate Day Fasting-improved Nash Required Activation Of E...mentioning

confidence: 99%

Esrra regulates Rplp1-mediated translation of lysosome proteins suppressed in non-alcoholic steatohepatitis and reversed by alternate day fasting

Tripathi

Gauthier

Sandireddy

et al. 2021

Preprint

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Although general translation declines during fasting, maintaining the translation of a subset or proteins is necessary for metabolic homeostasis and cell viability. Using unbiased proteome analysis of hepatic cells during starvation, we identified a novel pathway in which Esrra-mediated transcription of Rplp1-dependent translation of lysosomal proteins declined during early starvation and recovered after prolonged starvation to restore autophagy-lysosome function. Interestingly, hepatic Esrra-Rplp1-dependent translation rate of lysosomal proteins also was impaired in patients and mice with non-alcoholic steatohepatitis (NASH), and translational response to starvation was dysregulated in mice with NASH. Remarkably, activation of Esrra pharmacologically, genetically, or by alternate day fasting restored protein translation, increased expression of lysosomal proteins, induced autophagy, and reduced lipotoxicity, inflammation, and fibrosis in cell culture and in vivo models of NASH. Thus, hepatic Esrra is essential for ribosome-dependent translation of lysosomal proteins during starvation, and prevention of lipotoxicity and progression in NASH.Lay summaryFasting for weight loss improves non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH); however, the mechanism is not well understood. Our study shows that a nuclear protein, estrogen related receptor alpha (Esrra), increases ribosome-mediated translation of autophagy and lysosome proteins during chronic starvation to maintain essential metabolic pathways for cell survival. Surprisingly, this translational pathway is impaired during NASH with reduced lysosome-autophagy activity accompanied by increased inflammation and fibrosis gene expression in the liver. Pharmacologic, genetic and dietary activation of Esrra decreases lipid-mediated toxicity in liver cells as well as inflammation and fibrosis in livers from mice with NASH. These findings suggest that the Esrra-ribosome-lysosome pathway is important for liver response to fasting and NASH and thus may be a good therapeutic target for the treatment of NASH.

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A “short-cut” response of autophagy to oxidative stress: oxygen-dependent activity of a lysine demethylase guides the activity of ULK1 during hypoxia

Cited by 7 publications

References 7 publications

The Effects of Peanut Oligopeptides on Exercise-Induced Fatigue in Mice and Its Underlying Mechanism

The Effects of Peanut Oligopeptides on Exercise-Induced Fatigue in Mice and Its Underlying Mechanism

Ferroptosis, autophagy, tumor and immunity

Esrra regulates Rplp1-mediated translation of lysosome proteins suppressed in non-alcoholic steatohepatitis and reversed by alternate day fasting

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