Mechanistic insights into the inhibitory effects of palmitoylation on cytosolic thioredoxin reductase and thioredoxin

Qin, H.; Liang, Wei; Xu, Zhiyu; Ye, Fei; Li, Xiaoming; Zhong, Like

doi:10.1016/j.biochi.2014.12.018

Cited by 9 publications

(8 citation statements)

References 37 publications

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“…An increased autopalmitoylation of cytosolic thioredoxin reductase (TrxR1) and thioredoxin (hTrx1) occurs when incubated with high concentration of palmitoyl-CoA [77]. However, enhanced TrxR1/hTrx1 palmitoylation causes an inhibition of their activities and an induction of oxidative stress in liver cells [77]. This is consistent with the research that a HFD can induce TrxR1/hTrx1 palmitoylation and negatively impact these two critical antioxidant proteins in mouse liver [78].…”

Section: Lipid-induced Metabolic Disorders Via Palmitoylationsupporting

confidence: 84%

“…Over-nutrition like high glucose/palmitate leads to increased oxidative stress via palmitoylation. An increased autopalmitoylation of cytosolic thioredoxin reductase (TrxR1) and thioredoxin (hTrx1) occurs when incubated with high concentration of palmitoyl-CoA [77]. However, enhanced TrxR1/hTrx1 palmitoylation causes an inhibition of their activities and an induction of oxidative stress in liver cells [77].…”

Section: Lipid-induced Metabolic Disorders Via Palmitoylationmentioning

confidence: 99%

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Lipid-induced S-palmitoylation as a Vital Regulator of Cell Signaling and Disease Development

Qu¹,

Zhou²,

Wang³

et al. 2021

Int. J. Biol. Sci.

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Lipid metabolites are emerging as pivotal regulators of protein function and cell signaling. The availability of intracellular fatty acid is tightly regulated by glycolipid metabolism and may affect human body through many biological mechanisms. Recent studies have demonstrated palmitate, either from exogenous fatty acid uptake or de novo fatty acid synthesis, may serve as the substrate for protein palmitoylation and regulate protein function via palmitoylation. Palmitoylation, the most-studied protein lipidation, encompasses the reversible covalent attachment of palmitate moieties to protein cysteine residues. It controls various cellular physiological processes and alters protein stability, conformation, localization, membrane association and interaction with other effectors. Dysregulation of palmitoylation has been implicated in a plethora of diseases, such as metabolic syndrome, cancers, neurological disorders and infections. Accordingly, it could be one of the molecular mechanisms underlying the impact of palmitate metabolite on cellular homeostasis and human diseases. Herein, we explore the relationship between lipid metabolites and the regulation of protein function through palmitoylation. We review the current progress made on the putative role of palmitate in altering the palmitoylation of key proteins and thus contributing to the pathogenesis of various diseases, among which we focus on metabolic disorders, cancers, inflammation and infections, neurodegenerative diseases. We also highlight the opportunities and new therapeutics to target palmitoylation in disease development.

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Section: Lipid-induced Metabolic Disorders Via Palmitoylationsupporting

confidence: 84%

Section: Lipid-induced Metabolic Disorders Via Palmitoylationmentioning

confidence: 99%

Lipid-induced S-palmitoylation as a Vital Regulator of Cell Signaling and Disease Development

Qu¹,

Zhou²,

Wang³

et al. 2021

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…Amongst the 61 identifications common to both methods (Table 1) were a number of well-known palmitoyl-proteins, including the G protein subunit Gα o 42 , GAP43/neuromodulin 44 and trafficking protein particle complex 3 (TRAPPC3)/Bet3 45 . Notable also was thioredoxin, which is known to be palmitoylated 46 but has not previously been identified in proteomic studies. The E2 enzymes for ubiquitin and neural precursor cell expressed, developmentally down-regulated 8 (NEDD8) are likely false positives due to their use of a cysteine thioester which would be detected by these assays 47, 48 .…”

Section: Discussionmentioning

confidence: 99%

Analysis of the brain palmitoyl-proteome using both acyl-biotin exchange and acyl-resin-assisted capture methods

Edmonds

Geary

Doherty

et al. 2017

Sci Rep

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Palmitoylation is a reversible post-translational protein modification in which palmitic acid is added to cysteine residues, allowing association with different cellular membranes and subdomains. Recently, techniques have been developed to identify palmitoylation on a proteome-wide scale in order to reveal the full cellular complement of palmitoylated proteins. However, in the studies reported to date, there is considerable variation between the sets of identified palmitoyl-proteins and so there remains some uncertainty over what constitutes the definitive complement of palmitoylated proteins even in well-studied tissues such as brain. To address this issue, we used both acyl-biotin exchange and acyl-resin-assisted capture approaches using rat brain as a common protein source. The palmitoyl-proteins identified from each method by mass spectrometry were then compared with each other and previously published studies. There was generally good agreement between the two methods, although many identifications were unique to one method, indicating that at least some of the variability in published palmitoyl proteomes is due to methodological differences. By combining our new data with previous publications using mammalian cells/tissues, we propose a high confidence set of bona fide palmitoylated proteins in brain and provide a resource to help researchers prioritise candidate palmitoyl-proteins for investigation.

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“…Interestingly, as shown in Figure 4 It is notable that dysfunction of mitochondrial complex I has been recently linked to the loss of dopaminergic neurons and metabolic changes in the substantia nigra of mice, causing a human-like parkinsonism [48], and that low activity of mitochondrial complexes I, II and III has been reported in lymphocytes and platelets of PD patients [49,50]. Thioredoxin has antioxidant activity that protects dopaminergic neurons in animal models of PD [51], and its palmitoylation has been shown to modulate its activity [52,53]. Although the role of Tubulin Beta in PD is not well defined, its degradation seems to be regulated by Parkin [54], and its palmitoylation has been suggested [55].…”

Section: Altered Palmitoylation Levels Of Cortical Proteins In Pdmentioning

confidence: 99%

Altered Cortical Palmitoylation Induces Widespread Molecular Disturbances in Parkinson’s Disease

Cervilla-Martínez

Gotor

Wypijewski

et al. 2022

IJMS

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The relationship between Parkinson’s disease (PD), the second-most common neurodegenerative disease after Alzheimer’s disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, to better understand the role of protein palmitoylation in PD and the pathways altered in this disease, we analyzed the differential palmitoyl proteome (palmitome) in the cerebral cortex of PD patients compared to controls (n = 4 per group). Data-mining of the cortical palmitome from PD patients and controls allowed us to: (i) detect a set of 150 proteins with altered palmitoylation in PD subjects in comparison with controls; (ii) describe the biological pathways and targets predicted to be altered by these palmitoylation changes; and (iii) depict the overlap between the differential palmitome identified in our study with protein interactomes of the PD-linked proteins α-synuclein, LRRK2, DJ-1, PINK1, GBA and UCHL1. In summary, we partially characterized the altered palmitome in the cortex of PD patients, which is predicted to impact cytoskeleton, mitochondrial and fibrinogen functions, as well as cell survival. Our study suggests that protein palmitoylation could have a role in the pathophysiology of PD, and that comprehensive palmitoyl-proteomics offers a powerful approach for elucidating novel cellular pathways modulated in this neurodegenerative disease.

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Mechanistic insights into the inhibitory effects of palmitoylation on cytosolic thioredoxin reductase and thioredoxin

Cited by 9 publications

References 37 publications

Lipid-induced S-palmitoylation as a Vital Regulator of Cell Signaling and Disease Development

Lipid-induced S-palmitoylation as a Vital Regulator of Cell Signaling and Disease Development

Analysis of the brain palmitoyl-proteome using both acyl-biotin exchange and acyl-resin-assisted capture methods

Altered Cortical Palmitoylation Induces Widespread Molecular Disturbances in Parkinson’s Disease

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