Erastin promotes random-pattern skin flaps survival by inducing mTORC1-TFEB mediated autophagy DOI Creative Commons

Ximiao Chen,

Xuwei Zhu,

Yu Chen

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 116918 - 116918

Published: June 15, 2024

Random-pattern skin flaps are important method for reconstruction after defect; however, the distal end of is not easily viable due to inadequate nutrient supply. Erastin a well-established ferroptosis inducer, but our study found that low-dose erastin (2 μM) may reduce deficiency induced cell death in human umbilical vein endothelial cells (HUVECs). RNA-seq analysis suggested its role was related autophagy regulation. Follow-up studies have shown use inhibitors or knockdown TFEB HUVECs can both anti-apoptotic effect HUVECs. Mechanism demonstrated suppress mTORC1 and promote activity HUVECs, suggesting on survival under deprivation conditions regulated by mTORC1/TFEB. Subsequently, we evaluated random-pattern mice vivo. On postoperative day 7, observed significant increase flap area, blood perfusion, microvascular density treatment; also, treatment showed enhanced within ischemic region. In summary, demonstrates condition, effects relate mTORC1-TFEB medicated regulation, be potential therapy flaps.

Language: Английский

mTORC1 regulates the pyrimidine salvage pathway by controlling UCK2 turnover via the CTLH-WDR26 E3 ligase DOI Creative Commons
Brittany Q Pham, Sang Ah Yi, Alban Ordureau

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(1), P. 115179 - 115179

Published: Jan. 1, 2025

Language: Английский

Citations

1
mTOR controls ependymal cell differentiation by targeting the alternative cell cycle and centrosomal proteins DOI Creative Commons
Alexia Bankolé, Ayush Srivastava, ASM Shihavuddin

et al.

EMBO Reports, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Ependymal cells are multiciliated glial lining the ventricles of mammalian brain. Their differentiation from progenitor involves cell enlargement and progresses through centriole amplification phases ciliogenesis. These accompanied by sharp up-regulation mTOR Complex 1 activity (mTORC1), a master regulator macromolecule biosynthesis growth, whose function in ependymal is unknown. We demonstrate that mTORC1 inhibition rapamycin preserves pool reinforcing quiescence preventing alternative cycle progression for amplification. Overexpressing E2F4 MCIDAS circumvents mTORC1-regulated processes, enabling despite rapamycin, enhancing positive feedback. Acute treatment multicentriolar during late causes regrouping, indicating direct role dynamics. By phosphoproteomic phosphomutant analysis, we reveal mTORC1-mediated phosphorylation GAS2L1, centrosomal protein links actin microtubule cytoskeletons, participates disengagement. This multilayered sequential control development mTORC1, to centriolar function, has implications pathophysiological conditions like aging hydrocephalus-prone genetic diseases.

Language: Английский

Citations

0
AKR1B1-dependent fructose metabolism enhances malignancy of cancer cells DOI Creative Commons
Qing Zhao, Bing Han, Lu Wang

et al.

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: 31(12), P. 1611 - 1624

Published: Oct. 15, 2024

Abstract Fructose metabolism has emerged as a significant contributor to cancer cell proliferation, yet the underlying mechanisms and sources of fructose for cells remain incompletely understood. In this study, we demonstrate that can convert glucose into through process called AKR1B1 -mediated polyol pathway. Inhibiting endogenous production deletion dramatically suppressed glycolysis, resulting in reduced migration, inhibited growth, induction apoptosis cycle arrest. Conversely, acceleration overexpression been shown significantly enhance proliferation migration with increased S progression. Our findings highlight crucial role malignancy support need further investigation potential therapeutic target.

Language: Английский

Citations

3
Fructose: the sweet(er) side of the Warburg effect DOI Creative Commons
Christian Frezza

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: 31(11), P. 1395 - 1397

Published: Oct. 5, 2024

Language: Английский

Citations

2
Erastin promotes random-pattern skin flaps survival by inducing mTORC1-TFEB mediated autophagy DOI Creative Commons

Ximiao Chen,

Xuwei Zhu,

Yu Chen

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 116918 - 116918

Published: June 15, 2024

Random-pattern skin flaps are important method for reconstruction after defect; however, the distal end of is not easily viable due to inadequate nutrient supply. Erastin a well-established ferroptosis inducer, but our study found that low-dose erastin (2 μM) may reduce deficiency induced cell death in human umbilical vein endothelial cells (HUVECs). RNA-seq analysis suggested its role was related autophagy regulation. Follow-up studies have shown use inhibitors or knockdown TFEB HUVECs can both anti-apoptotic effect HUVECs. Mechanism demonstrated suppress mTORC1 and promote activity HUVECs, suggesting on survival under deprivation conditions regulated by mTORC1/TFEB. Subsequently, we evaluated random-pattern mice vivo. On postoperative day 7, observed significant increase flap area, blood perfusion, microvascular density treatment; also, treatment showed enhanced within ischemic region. In summary, demonstrates condition, effects relate mTORC1-TFEB medicated regulation, be potential therapy flaps.

Language: Английский

Citations

0