Nudix hydrolase NUDT19 regulates mitochondrial function and ATP production in murine hepatocytes

Görigk, Sarah; Ouwens, D.M.; Kuhn, Tanja; Altenhofen, Delsi; Binsch, Christian; Damen, Mareike; Khuong, Jenny Minh-An; Kaiser, Katharina; Knebel, Birgit; Vogel, Heike; Schürmann, Annette; Chadt, Alexandra; Al-Hasani, Hadi

doi:10.1016/j.bbalip.2022.159153

Cited by 5 publications

(3 citation statements)

References 58 publications

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“…ALKBH7, ACSF3, MLYCD, and CRAT have been reported to be direct regulators of NAFLD (Derdak et al, 2013 ; Solberg et al, 2013 ; Sun et al, 2020 ; Wallace et al, 2018 ; Wang et al, 2014a ), while NUDT19, MMUT, and ALAS1 have been thought to be associated with lipid metabolism (Gorigk et al, 2022 ; Lian et al, 2018 ; Luciani and Devuyst, 2020 ; Wang et al, 2014a ; Yao et al, 2018 ). To understand their role in lipid metabolism in detail, we drew a metabolic pathway based on existing knowledge (Fig.…”

Section: Resultsmentioning

confidence: 99%

NME4 mediates metabolic reprogramming and promotes nonalcoholic fatty liver disease progression

Xie,

Yuan,

Sui

et al. 2023

EMBO Rep

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Nonalcoholic fatty liver disease (NAFLD) is mainly characterized by excessive fat accumulation in the liver, and it is associated with liver-related complications and adverse systemic diseases. NAFLD has become the most prevalent liver disease; however, effective therapeutic agents for NAFLD are still lacking. We combined clinical data with proteomics and metabolomics data, and found that the mitochondrial nucleoside diphosphate kinase NME4 plays a central role in mitochondrial lipid metabolism. Nme4 is markedly upregulated in mice fed with high-fat diet, and its expression is positively correlated with the level of steatosis. Hepatic deletion of Nme4 suppresses the progression of hepatic steatosis. Further studies demonstrated that NME4 interacts with several key enzymes in coenzyme A (CoA) metabolism and increases the level of acetyl-CoA and malonyl-CoA, which are the major lipid components of the liver in NAFLD. Increased level of acetyl-CoA and malonyl-CoA lead to increased triglyceride levels and lipid accumulation in the liver. Taken together, these findings reveal that NME4 is a critical regulator of NAFLD progression and a potential therapeutic target for NAFLD.

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Section: Resultsmentioning

confidence: 99%

NME4 mediates metabolic reprogramming and promotes nonalcoholic fatty liver disease progression

Xie,

Yuan,

Sui

et al. 2023

EMBO Rep

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show abstract

“…NME4 regulates coenzyme A metabolism and lipid accumulation by interacting with the key enzymes in the pathway. ALKBH7, ACSF3, MLYCD and CRAT have been reported to be direct regulators of NAFLD 39,40,41,42,43 , while NUDT19, MMUT and ALAS1 have been thought to be associated with lipid metabolism 42,44,45,46,47 . To understand their role in lipid metabolism in detail, we drew a metabolic pathway based on existing knowledge (Fig.…”

Section: Resultsmentioning

confidence: 99%

The Mitochondrial Nucleoside Diphosphate Kinase NME4 Mediates Metabolic Reprogramming and Plays a Key Role in Nonalcoholic Fatty Liver Disease Progression

Xie

et al. 2023

Preprint

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Nonalcoholic fatty liver disease (NAFLD) is mainly characterized by excessive fat accumulation in the liver, and it is associated with liver-related complications and adverse systemic diseases. NAFLD has become the most prevalent liver disease; however, effective therapeutic agents for NAFLD are still lacking. We combined clinical data with proteomics and metabolomics data, and found that the mitochondrial nucleoside diphosphate kinase NME4 plays a central role in mitochondrial lipid metabolism. Nme4 is markedly upregulated in mice fed with high-fat diet, and its expression is positively correlated with the level of steatosis. Hepatic deletion of Nme4 suppresses the progression of hepatic steatosis. Further studies demonstrated that NME4 interacts with several key enzymes in coenzyme A metabolism and increases the level of acetyl-CoA and malonyl-CoA, which are the major lipid component of the liver in NAFLD. Increased acetyl-CoA and malonyl-CoA levels lead to increased triglyceride levels and lipid accumulation in the liver. Taken together, these findings reveal that NME4 is a critical regulator of NAFLD progression and a potential therapeutic target for NAFLD.

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“…Ces2e and Ces1 are carboxylesterases that play an important role in exogenous ester drug metabolism and endogenous lipid metabolism ( Lian et al, 2018 ), and their expression levels showed an increasing trend in this study. In addition, the disruption in the expression levels of the proteins Nudt19, Lonp2, and PEX16, which are related to mitochondrial and peroxisomal productivity ( Wu et al, 2018 ; Burkhart et al, 2019 ; Görigk et al, 2022 ), also reflected the metabolic disorders caused by AAI.…”

Section: Discussionmentioning

confidence: 99%

Delineation of renal protein profiles in aristolochic acid I-induced nephrotoxicity in mice by label-free quantitative proteomics

Liu,

Wu,

Peng

et al. 2024

Front. Pharmacol.

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Introduction: Aristolochic acid nephropathy (AAN) is a kidney injury syndrome caused by aristolochic acids exposure. Our study used label-free quantitative proteomics to delineate renal protein profiles and identify key proteins after exposure to different doses of aristolochic acid I (AAI).Methods: Male C57BL/6 mice received AAI (1.25 mg/kg/d, 2.5 mg/kg/d, or 5 mg/kg/d) or vehicle for 5 days.Results and discussion: The results showed that AAI induced dose-dependent nephrotoxicity. Differences in renal protein profiles between the control and AAI groups increased with AAI dose. Comparing the control with the low-, medium-, and high-dose AAI groups, we found 58, 210, and 271 differentially expressed proteins, respectively. Furthermore, protein-protein interaction network analysis identified acyl-CoA synthetase medium-chain family member 3 (Acsm3), cytochrome P450 family 2 subfamily E member 1 (Cyp2e1), microsomal glutathione S-transferase 1 (Mgst1), and fetuin B (Fetub) as the key proteins. Proteomics revealed that AAI decreased Acsm3 and Cyp2e1 while increasing Mgst1 and Fetub expression in mice kidneys, which was further confirmed by Western blotting. Collectively, in AAI-induced nephrotoxicity, renal protein profiles were dysregulated and exacerbated with increasing AAI dose. Acsm3, Cyp2e1, Mgst1, and Fetub may be the potential therapeutic targets for AAN.

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Nudix hydrolase NUDT19 regulates mitochondrial function and ATP production in murine hepatocytes

Cited by 5 publications

References 58 publications

NME4 mediates metabolic reprogramming and promotes nonalcoholic fatty liver disease progression

NME4 mediates metabolic reprogramming and promotes nonalcoholic fatty liver disease progression

The Mitochondrial Nucleoside Diphosphate Kinase NME4 Mediates Metabolic Reprogramming and Plays a Key Role in Nonalcoholic Fatty Liver Disease Progression

Delineation of renal protein profiles in aristolochic acid I-induced nephrotoxicity in mice by label-free quantitative proteomics

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