SENP1-Sirt3 signaling promotes α-ketoglutarate production during M2 macrophage polarization

Wei, Zhou; Hu, Gaolei; He, Jianli; Wang, Tianshi; Zuo, Yongchun; Cao, Ying; Zheng, Quan; Tang, Jun; Ma, Jiao; Cai, Rong; Chen, Yalan; Fan, Qiuju; Dong, Baijun; Tan, Hongsheng; Wang, Qi; Xue, Wei; Cheng, Jinke

doi:10.1016/j.celrep.2022.110660

Cited by 49 publications

(30 citation statements)

References 59 publications

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“…SUMO‐specific protease SENP1 activates SIRT3 via de‐SUMOylation to augment M2 macrophage polarization, through the accumulation of α KG in a glutaminolysis‐dependent manner. [ 50 ] More specific information and the underlying mechanisms of SIRT3 in cartilage–bone–synovium crosstalk will be explored in our future work.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3‐COX4I2 Axis Attenuates Osteoarthritis Progression

et al. 2023

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Mitochondrial homeostasis is of great importance for cartilage integrity and associated with the progression of osteoarthritis (OA); however, the underlying mechanisms are unknown. This study aims to investigate the role of mitochondrial deacetylation reaction and investigate the mechanistic relationship OA development. Silent mating type information regulation 2 homolog 3 (SIRT3) expression has a negative correlation with the severity of OA in both human arthritic cartilage and mice inflammatory chondrocytes. Global SIRT3 deletion accelerates pathological phenotype in post‐traumatic OA mice, as evidenced by cartilage extracellular matrix collapse, osteophyte formation, and synovial macrophage M1 polarization. Mechanistically, SIRT3 prevents OA progression by targeting and deacetylating cytochrome c oxidase subunit 4 isoform 2 (COX4I2) to maintain mitochondrial homeostasis at the post‐translational level. The activation of SIRT3 by honokiol restores cartilage metabolic equilibrium and protects mice from the development of post‐traumatic OA. Collectively, the loss of mitochondrial SIRT3 is essential for the development of OA, whereas SIRT3‐mediated proteins deacetylation of COX4I2 rescues OA‐impaired mitochondrial respiratory chain functions to improve the OA phenotype. Herein, the induction of SIRT3 provides a novel therapeutic candidate for OA treatment.

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Section: Discussionmentioning

confidence: 99%

Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3‐COX4I2 Axis Attenuates Osteoarthritis Progression

et al. 2023

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“…Previous studies have shown that IL‐1 suppressed mitochondrial fatty acid oxidation to drive tissue‐specific inflammation 192,193 . IL‐4 was reported to promote mitochondrial glutaminolysis and α‐ketoglutarate production in macrophages 194 …”

Section: Mechanisms Of Remodeling Host Metabolism By Sars‐cov‐2mentioning

confidence: 99%

“… 192 , 193 IL‐4 was reported to promote mitochondrial glutaminolysis and α‐ketoglutarate production in macrophages. 194 …”

Section: Mechanisms Of Remodeling Host Metabolism By Sars‐cov‐2mentioning

confidence: 99%

COVID‐19 metabolism: Mechanisms and therapeutic targets

Wang

Cao

Zhang³

et al. 2022

MedComm

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) dysregulates antiviral signaling, immune response, and cell metabolism in human body. Viral genome and proteins hijack host metabolic network to support viral biogenesis and propagation. However, the regulatory mechanism of SARS‐CoV‐2‐induced metabolic dysfunction has not been elucidated until recently. Multiomic studies of coronavirus disease 2019 (COVID‐19) revealed an intensive interaction between host metabolic regulators and viral proteins. SARS‐CoV‐2 deregulated cellular metabolism in blood, intestine, liver, pancreas, fat, and immune cells. Host metabolism supported almost every stage of viral lifecycle. Strikingly, viral proteins were found to interact with metabolic enzymes in different cellular compartments. Biochemical and genetic assays also identified key regulatory nodes and metabolic dependencies of viral replication. Of note, cholesterol metabolism, lipid metabolism, and glucose metabolism are broadly involved in viral lifecycle. Here, we summarized the current understanding of the hallmarks of COVID‐19 metabolism. SARS‐CoV‐2 infection remodels host cell metabolism, which in turn modulates viral biogenesis and replication. Remodeling of host metabolism creates metabolic vulnerability of SARS‐CoV‐2 replication, which could be explored to uncover new therapeutic targets. The efficacy of metabolic inhibitors against COVID‐19 is under investigation in several clinical trials. Ultimately, the knowledge of SARS‐CoV‐2‐induced metabolic reprogramming would accelerate drug repurposing or screening to combat the COVID‐19 pandemic.

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“…SIRT2-deficient mice developed severe colitis, and the related increase in the inflammatory response resulted from a reduction in M2 polarization and NF-κB activation ( 71 ). SENP1-SIRT3 signaling contributes to αKG accumulation via glutaminolysis and promotes M2 polarization ( 72 ). Supplementary SIRT4 treatment or induced SIRT4 overexpression significantly enhanced aggrecan and collagen II, antioxidant enzyme, expression and suppressed the inflammatory response and ROS production ( 45 ).…”

Section: Sirts and Inflammationmentioning

confidence: 99%

Sirtuins in osteoarthritis: current understanding

et al. 2023

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Osteoarthritis (OA) is a common disease characterized by severe chronic joint pain, that imposes a large burden on elderly people. OA is a highly heterogeneous disease, and multiple etiologies contribute to its progression. Sirtuins (SIRTs) are Class III histone deacetylases (HDACs) that regulate a comprehensive range of biological processes such as gene expression, cell differentiation, and organism development, and lifespan. Over the past three decades, increasing evidence has revealed that SIRTs are not only important energy sensors but also protectors against metabolic stresses and aging, and an increasing number of studies have focused on the functions of SIRTs in OA pathogenesis. In this review, we illustrate the biological functions of SIRTs in OA pathogenesis from the perspectives of energy metabolism, inflammation, autophagy and cellular senescence. Moreover, we offer insights into the role played by SIRTs in regulating circadian rhythm, which has recently been recognized to be crucial in OA development. Here, we provide the current understanding of SIRTs in OA to guide a new direction for OA treatment exploration.

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SENP1-Sirt3 signaling promotes α-ketoglutarate production during M2 macrophage polarization

Cited by 49 publications

References 59 publications

Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3‐COX4I2 Axis Attenuates Osteoarthritis Progression

Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3‐COX4I2 Axis Attenuates Osteoarthritis Progression

COVID‐19 metabolism: Mechanisms and therapeutic targets

Sirtuins in osteoarthritis: current understanding

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