PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation

Fu, Gengfeng; Li, Shiting; Jiang, Zetan; Mao, Qianguo; Xiong, Nanchi; Li, Xiang; Hao, Yijie; Zhang, Huafeng

doi:10.3724/abbs.2023155

Cited by 4 publications

(3 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Malic enzyme 1 (ME1) is an NADP (+)-dependent enzyme that links glycolysis and the TCA cycle. Using immunoprecipitation and mass spectrum data, Fu and colleagues demonstrated that deacetylation of phosphoglycerate mutase 5 boosts the activity of the ME1, thereby stimulating lipid synthesis and the proliferation of liver cancer cells [ 164 ]. Metabolic rewiring of glycoxenogenic enzyme phosphoenolpyruvate carboxykinase 1 (PCK1) disrupts hexosamine synthesis pathway-mediated O-GlcNAcylation and induces cataplerosis in the TCA cycle [ 165 , 166 ].…”

Section: Interactions Between Epigenetic Modifications and Hcc Cell M...mentioning

confidence: 99%

Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

Li,

Wang,

Zhao

et al. 2024

Metabolites

View full text Add to dashboard Cite

Epigenetic and metabolic reprogramming alterations are two important features of tumors, and their reversible, spatial, and temporal regulation is a distinctive hallmark of carcinogenesis. Epigenetics, which focuses on gene regulatory mechanisms beyond the DNA sequence, is a new entry point for tumor therapy. Moreover, metabolic reprogramming drives hepatocellular carcinoma (HCC) initiation and progression, highlighting the significance of metabolism in this disease. Exploring the inter-regulatory relationship between tumor metabolic reprogramming and epigenetic modification has become one of the hot directions in current tumor metabolism research. As viral etiologies have given way to metabolic dysfunction-associated steatotic liver disease (MASLD)-induced HCC, it is urgent that complex molecular pathways linking them and hepatocarcinogenesis be explored. However, how aberrant crosstalk between epigenetic modifications and metabolic reprogramming affects MASLD-induced HCC lacks comprehensive understanding. A better understanding of their linkages is necessary and urgent to improve HCC treatment strategies. For this reason, this review examines the interwoven landscape of molecular carcinogenesis in the context of MASLD-induced HCC, focusing on mechanisms regulating aberrant epigenetic alterations and metabolic reprogramming in the development of MASLD-induced HCC and interactions between them while also updating the current advances in metabolism and epigenetic modification-based therapeutic drugs in HCC.

show abstract

Section: Interactions Between Epigenetic Modifications and Hcc Cell M...mentioning

confidence: 99%

Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

Li,

Wang,

Zhao

et al. 2024

Metabolites

View full text Add to dashboard Cite

show abstract

“…Additionally, Pgam5 interacts with several key proteins, such as Parkin and PINK1, which are integral to mitochondrial quality control mechanisms. Recent studies have reported that Pgam5 affects liver cancer proliferation [35] and participates into the hepatic inflammation [36]. Besides, non-alcoholic steatohepatitis is also under the control of Pgam5 in a high fat/high fructose diet-treated mouse model [29].…”

Section: Introductionmentioning

confidence: 99%

Phosphoglycerate mutase 5 aggravates alcoholic liver disease through disrupting VDAC-1-dependent mitochondrial integrity

Xia,

Yu,

Chen

et al. 2024

Int. J. Med. Sci.

View full text Add to dashboard Cite

Alcoholic liver disease (ALD) poses a substantial global health challenge, with its pathogenesis deeply rooted in mitochondrial dysfunction. Our study explores the pivotal roles of Phosphoglycerate mutase family member 5 (Pgam5) and Voltage-Dependent Anion Channel 1 (VDAC1) in the progression of ALD, providing novel insights into their interplay and impact on mitochondrial integrity. We demonstrate that Pgam5 silencing preserves hepatocyte viability and attenuates ethanol-induced apoptosis, underscoring its detrimental role in exacerbating hepatocyte dysfunction. Pgam5's influence extends to the regulation of VDAC1 oligomerization, a key process in mitochondrial permeability transition pore (mPTP) opening, mitochondrial swelling, and apoptosis initiation. Notably, the inhibition of VDAC1 oligomerization through Pgam5 silencing or pharmacological intervention (VBIT-12) significantly preserves mitochondrial function, evident in the maintenance of mitochondrial membrane potential and reduced reactive oxygen species (ROS) production. In vivo experiments using hepatocyte-specific Pgam5 knockout (Pgam5 hKO ) and control mice reveal that Pgam5 deficiency mitigates ethanol-induced liver histopathology, inflammation, lipid peroxidation, and metabolic disorder, further supporting its role in ALD progression. Our findings highlight the critical involvement of Pgam5 and VDAC1 in mitochondrial dysfunction in ALD, suggesting potential therapeutic targets. While promising, these findings necessitate further research, including human studies, to validate their clinical applicability and explore broader implications in liver diseases. Overall, our study provides a significant advancement in understanding ALD pathophysiology, paving the way for novel therapeutic strategies targeting mitochondrial pathways in ALD.

show abstract

“…Sirtuin 2 (SIRT2), a NAD + -dependent deacetylase, predominantly resides in the cytoplasm but also exists in mitochondria and the nucleus 14 . Recent studies highlight its significant role in various liver diseases, including hepatocellular carcinoma 15 , alcoholic liver disease 16 , and non-alcoholic fatty liver disease17. Tang et al demonstrated that SIRT2 binds to liver kinase B1 (LKB1), deacetylating it at lysine 48, thereby enhancing LKB1 phosphorylation and the subsequent LKB1-AMPK signaling activation 18 .…”

Section: Introductionmentioning

confidence: 99%

The SIRT2-AMPK axis regulates autophagy induced by acute liver failure

Zhang,

Guo,

Shi

et al. 2024

Sci Rep

View full text Add to dashboard Cite

This study explores the role of SIRT2 in regulating autophagy and its interaction with AMPK in the context of acute liver failure (ALF). This study investigated the effects of SIRT2 and AMPK on autophagy in ALF mice and TAA-induced AML12 cells. The results revealed that the liver tissue in ALF model group had a lot of inflammatory cell infiltration and hepatocytes necrosis, which were reduced by SIRT2 inhibitor AGK2. In comparison to normal group, the level of SIRT2, P62, MDA, TOS in TAA group were significantly increased, which were decreased in AGK2 treatment. Compared with normal group, the expression of P-PRKAA1, Becilin1 and LC3B-II was decreased in TAA group. However, AGK2 enhanced the expression of P-PRKAA1, Becilin1 and LC3B-II in model group. Overexpression of SIRT2 in AML12 cell resulted in decreased P-PRKAA1, Becilin1 and LC3B-II level, enhanced the level of SIRT2, P62, MDA, TOS. Overexpression of PRKAA1 in AML12 cell resulted in decreased SIRT2, TOS and MDA level and triggered more autophagy. In conclusion, the data suggested the link between AMPK and SIRT2, and reveals the important role of AMPK and SIRT2 in autophagy on acute liver failure.

show abstract

PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation

Cited by 4 publications

References 36 publications

Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

Phosphoglycerate mutase 5 aggravates alcoholic liver disease through disrupting VDAC-1-dependent mitochondrial integrity

The SIRT2-AMPK axis regulates autophagy induced by acute liver failure

Contact Info

Product

Resources

About