The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient "Yin-Yang" theory and modern immunology DOI Creative Commons
Huantian Cui, Ning Wang, Hanzhou Li

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 6, 2024

Abstract The changes in T regulatory cell (Treg) and helper (Th) 17 ratios holds paramount importance ensuring internal homeostasis disease progression. Recently, novel subsets of Treg Th17, namely IL-17-producing IL-10-producing Th17 have been identified. are widely considered as the intermediates during Treg/Th17 transformation. These “bi-functional” cells exhibit plasticity demonstrated with important roles multiple physiological functions processes. Yin Yang represent opposing aspects phenomena according to ancient Chinese philosophy “Yin-Yang” theory. Furthermore, can transform into Yang, vice versa, under specific conditions. This theory has used describe contrasting immune molecules. Therefore, immune-activating populations (Th17, M1 macrophage, etc.) overreaction (inflammation, autoimmunity) be while immunosuppressive (Treg, M2 immunosuppression (tumor, immunodeficiency) Yin. However, another connotation theory, conversion between rarely documented studies. discovery enriches meaning further promotes relationship modern immunology. Besides, illustrating mechanisms governing their differentiation provides valuable insights underlying dynamically changing statement health diseases.

Language: Английский

Autophagy and autophagy-related pathways in cancer DOI Open Access
Jayanta Debnath, Noor Gammoh, Kevin M. Ryan

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(8), P. 560 - 575

Published: March 2, 2023

Language: Английский

Citations

669
Copper-dependent autophagic degradation of GPX4 drives ferroptosis DOI Creative Commons
Qian‐Li Xue, Yan Ding, Xi Chen

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 19(7), P. 1982 - 1996

Published: Jan. 9, 2023

Ferroptosis is a type of iron-dependent regulated cell death characterized by unrestricted lipid peroxidation and membrane damage. Although GPX4 (glutathione peroxidase 4) plays master role in blocking ferroptosis eliminating phospholipid hydroperoxides, the regulation remains poorly understood. Here, we report an unexpected for copper promoting ferroptotic death, but not cuproptosis, inducing macroautophagic/autophagic degradation GPX4. Copper chelators reduce sensitivity do inhibit other types such as apoptosis, necroptosis, alkaliptosis. Conversely, exogenous increases ubiquitination formation aggregates directly binding to protein cysteines C107 C148. TAX1BP1 (Tax1 1) then acts autophagic receptor subsequent response stress. Consequently, enhances ferroptosis-mediated tumor suppression mouse model pancreatic cancer tumor, whereas attenuate experimental acute pancreatitis associated with ferroptosis. Taken together, these findings provide new insights into link between metal stress autophagy-dependent death.Abbreviations: CALCOCO2, calcium coiled-coil domain 2; GPX4, glutathione 4; MAP1LC3A/B, microtubule 1 light chain 3 alpha/beta; MPO, myeloperoxidase; NCOA4, nuclear coactivator OPTN, optineurin; PDAC, ductal adenocarcinoma; RIPK1, interacting serine/threonine kinase 1; ROS, reactive oxygen species; SLC40A1, solute carrier family 40 member SQSTM1, sequestosome TAX1BP1, Tax1 TEPA, tetraethylenepentamine; TM, tetrathiomolybdate.

Language: Английский

Citations

312
Mitochondria-associated programmed cell death as a therapeutic target for age-related disease DOI Creative Commons
Thanh Tùng Nguyễn, Shibo Wei, Ha Nguyen Thi Thu

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(8), P. 1595 - 1619

Published: Aug. 23, 2023

Abstract Mitochondria, ubiquitous double-membrane-bound organelles, regulate energy production, support cellular activities, harbor metabolic pathways, and, paradoxically, mediate cell fate. Evidence has shown mitochondria as points of convergence for diverse death-inducing pathways that trigger the various mechanisms underlying apoptotic and nonapoptotic programmed death. Thus, dysfunctional eventually lead or contribute to age-related diseases, such neurodegenerative, cardiovascular diseases. mitochondrion-associated death-based treatments show great therapeutic potential, providing novel insights in clinical trials. This review discusses mitochondrial quality control networks with activity triggered by stimuli maintain homeostasis via mitohormesis, unfolded protein response, mitophagy. The also presents details on forms mitochondria-associated death, including apoptosis, necroptosis, ferroptosis, pyroptosis, parthanatos, paraptosis, highlights their involvement disease pathogenesis, collectively suggesting directions further research.

Language: Английский

Citations

118
Mitochondrial degradation: Mitophagy and beyond DOI Creative Commons
Louise Uoselis, Thanh Ngoc Nguyen, Michael Lazarou

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(19), P. 3404 - 3420

Published: Oct. 1, 2023

Mitochondria are central hubs of cellular metabolism that also play key roles in signaling and disease. It is therefore fundamentally important mitochondrial quality activity tightly regulated. Mitochondrial degradation pathways contribute to control networks can regulate the metabolic profile mitochondria ensure homeostasis. Here, we cover many varied ways which cells degrade or remove their unwanted mitochondria, ranging from mitophagy extrusion. The molecular signals driving these discussed, including physiological contexts under different engaged.

Language: Английский

Citations

113
Crosstalk between mitochondrial biogenesis and mitophagy to maintain mitochondrial homeostasis DOI Creative Commons
Lei Liu, Yanjun Li, Guo Chen

et al.

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: Oct. 12, 2023

Mitochondrial mass and quality are tightly regulated by two essential opposing mechanisms, mitochondrial biogenesis (mitobiogenesis) mitophagy, in response to cellular energy needs other environmental cues. Great strides have been made uncover key regulators of these complex processes. Emerging evidence has shown that there exists a tight coordination between mitophagy mitobiogenesis, their defects may cause many human diseases. In this review, we will first summarize the recent advances discovery molecular regulations mitobiogenesis then focus on mechanism signaling pathways involved simultaneous regulation tissue or cultured cells needs, stress, pathophysiological conditions. Further studies crosstalk processes at level provide better understanding how cell maintains optimal fitness function under physiological conditions, which holds promise for fighting aging aging-related

Language: Английский

Citations

80
Oxidative stress as a key modulator of cell fate decision in osteoarthritis and osteoporosis: a narrative review DOI Creative Commons
Jana Riegger, Astrid Schoppa,

Leonie Ruths

et al.

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: Sept. 30, 2023

Abstract During aging and after traumatic injuries, cartilage bone cells are exposed to various pathophysiologic mediators, including reactive oxygen species (ROS), damage-associated molecular patterns, proinflammatory cytokines. This detrimental environment triggers cellular stress subsequent dysfunction, which not only contributes the development of associated diseases, that is, osteoporosis osteoarthritis, but also impairs regenerative processes. To counter ROS-mediated reduce overall tissue damage, possess diverse defense mechanisms. However, antioxidative capacities limited thus ROS accumulation can lead aberrant cell fate decisions, have adverse effects on homeostasis. In this narrative review, we address oxidative as a major driver processes in bone, senescence, misdirected differentiation, death, mitochondrial impaired mitophagy by illustrating consequences homeostasis regeneration. Moreover, elaborate mechanisms, with particular focus response mitophagy, briefly discuss respective therapeutic strategies improve protection.

Language: Английский

Citations

76
The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease DOI

Claire Goul,

Roberta Peruzzo, Roberto Zoncu

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(12), P. 857 - 875

Published: Aug. 23, 2023

Language: Английский

Citations

72
The hallmarks of cancer immune evasion DOI
Claudia Galassi, Timothy A. Chan, Ilio Vitale

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(11), P. 1825 - 1863

Published: Oct. 10, 2024

Language: Английский

Citations

70
Evidence of Flavonoids on Disease Prevention DOI Creative Commons
Meng Li,

Mengqi Qian,

Qian Jiang

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 527 - 527

Published: Feb. 20, 2023

A growing body of evidence highlights the properties flavonoids in natural foods for disease prevention. Due to their antioxidative, anti-inflammatory, and anti-carcinogenic activities, have been revealed benefit skeletal muscle, liver, pancreas, adipocytes, neural cells. In this review, we introduced basic classification, sources, biochemical flavonoids, then summarize experimental results underlying molecular mechanisms concerning effects flavonoid consumption on obesity, cancers, neurogenerative diseases that greatly threaten public health. Especially, dosage duration intervening these are discussed, which might guide healthy dietary habits people different physical status.

Language: Английский

Citations

62
International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis DOI Creative Commons
Xin Chen,

Andrey S. Tsvetkov,

Han‐Ming Shen

et al.

Autophagy, Journal Year: 2024, Volume and Issue: 20(6), P. 1213 - 1246

Published: March 6, 2024

Macroautophagy/autophagy is a complex degradation process with dual role in cell death that influenced by the types are involved and stressors they exposed to. Ferroptosis an iron-dependent oxidative form of characterized unrestricted lipid peroxidation context heterogeneous plastic mechanisms. Recent studies have shed light on involvement specific autophagy (e.g. ferritinophagy, lipophagy, clockophagy) initiating or executing ferroptotic through selective anti-injury proteins organelles. Conversely, other forms reticulophagy lysophagy) enhance cellular defense against damage. Dysregulated autophagy-dependent ferroptosis has implications for diverse range pathological conditions. This review aims to present updated definition ferroptosis, discuss influential substrates receptors, outline experimental methods, propose guidelines interpreting results.

Language: Английский

Citations

59