TRAP1: A Metabolic Hub Linking Aging Pathophysiology to Mitochondrial S-Nitrosylation

Faienza, Fiorella; Rizza, Salvatore; Giglio, Paola; Filomeni, Giuseppe

doi:10.3389/fphys.2020.00340

Cited by 8 publications

(10 citation statements)

References 38 publications

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“…It reduces the level of ROS and inhibits the opening of mitochondrial permeability transition pores, both of which play an important role in the process of apoptosis. 9 , 10 This is closely related to the role of TRAP1 in metabolism, which can control the flow of electrons in the respiratory complex of the electron transport chain. 11 Through this process, TRAP1 can reshape metabolism by down-regulating mitochondrial oxidative phosphorylation and promoting glycolysis, which is the main metabolic mode of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

TRAP1 Shows Clinical Significance in the Early Diagnosis of Small Cell Lung Cancer

Li¹,

Xu²,

Chen³

et al. 2021

JIR

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Purpose To explore the clinical significance of tumor necrosis factor receptor-associated protein (TRAP1), mitotic arrest deficient 2 (mad2) and anti-nuclear mitotic spindle apparatus antibody (MSA) in the diagnosis of small cell lung cancer (SCLC). Patients and Methods Serum concentrations of TRAP1 and MSA were determined by enzyme-linked immunosorbent assay (ELISA), including SCLC group (Num.=86), non-small cell lung cancer (NSCLC) group (Num.=105), pulmonary nodules (PN) group (Num.=94), and 60 healthy subjects as control group (Num.=60). Whereas fluorescence quantitative PCR (qt-PCR) method was used to detect the expression of mad2. Results The expression of TRAP1 was low in SCLC and NSCLC compared with the other two groups, and was the lowest in SCLC, which was negatively correlated with the occurrence of the disease (P<0.05); the sensitivity and specificity of TRAP1 for SCLC were 75.29%, 93.33%, and the area under SCLC curve was 0.903; compared with the other three groups, the level of MSA was the highest in the SCLC, and the results were significantly different (P<0.05), while the area under the SCLC curve was 0.856, and the sensitivity and specificity were 62.78% and 95.24%, respectively. Mad2 is overexpressed in SCLC, but not in PN. The area under the SCLC curve is 0.835, and the sensitivity and specificity are 56.98% and 92.38%; TRAP1 levels are negatively correlated with SCLC tumor stage, the level of TRAP1 was significantly lower in stage III–IV than in stage I–II (P<0.05); combined analysis of TRAP1 and MAD2 and MSA showed that the sensitivity and specificity for SCLS were 95.35% and 99.05%, respectively. Conclusion TRAP1 is of great value in the early diagnosis of SCLC as well as differential diagnosis with NSCLC. TRAP1 combined with MAD2 and MSA improved the sensitivity and specificity and provided a new idea for the clinical diagnosis of SCLC.

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Section: Discussionmentioning

confidence: 99%

TRAP1 Shows Clinical Significance in the Early Diagnosis of Small Cell Lung Cancer

Li¹,

Xu²,

Chen³

et al. 2021

JIR

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“…The human TRAP1 gene locus resides on chromosome 16p13, spans 60 kb, and includes 18 exons. The main TRAP1 transcript composed of 2,112 bp, encodes a protein of 704 amino acids [ 9 ] containing three major domains: NTD, MD and CTD ( Figure 1 ), as previously mentioned [ 2 , 3 , 10 ].…”

Section: Trap1 Molecular Structurementioning

confidence: 99%

“…The prototypic HSP90 family member has three structural domains, namely, an N-terminal domain (NTD) responsible for ATP binding, a middle domain (MD) which is important for binding clients and the ɣ-phosphate of ATP, and a C-terminal domain (CTD) responsible for dimerization. Like other chaperones, HSP90 family members are important for the folding of client protein substrates, as well as the degradation of the misfolded proteins [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…TRAP1 was extensively studied in oncology once TRAP1 is selectively upregulated in several human tumors and this is correlated with malignant progression, metastatic potential, and resistance to chemotherapy [ 3 ]. For those reasons, TRAP1 is emerging as a therapeutic target with several researchers attempting to develop TRAP1 specific inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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TRAP1 in Oxidative Stress and Neurodegeneration

et al. 2021

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Tumor necrosis factor receptor-associated protein 1 (TRAP1), also known as heat shock protein 75 (HSP75), is a member of the heat shock protein 90 (HSP90) chaperone family that resides mainly in the mitochondria. As a mitochondrial molecular chaperone, TRAP1 supports protein folding and contributes to the maintenance of mitochondrial integrity even under cellular stress. TRAP1 is a cellular regulator of mitochondrial bioenergetics, redox homeostasis, oxidative stress-induced cell death, apoptosis, and unfolded protein response (UPR) in the endoplasmic reticulum (ER). TRAP1 has attracted increasing interest as a therapeutical target, with a special focus on the design of TRAP1 specific inhibitors. Although TRAP1 was extensively studied in the oncology field, its role in central nervous system cells, under physiological and pathological conditions, remains largely unknown. In this review, we will start by summarizing the biology of TRAP1, including its structure and related pathways. Thereafter, we will continue by debating the role of TRAP1 in the maintenance of redox homeostasis and protection against oxidative stress and apoptosis. The role of TRAP1 in neurodegenerative disorders will also be discussed. Finally, we will review the potential of TRAP1 inhibitors as neuroprotective drugs.

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“…More recently, it was proposed that S-nitrosylation of the Cys 501 residue of TRAP1 favors its loss of activity and the chaperone degradation [36]. Also, this fact may have relevance in aging and age-related diseases such as neurodegeneration [37], processes that are closely related to pathological states due to mitochondrial dysfunctions. Whether or not β−amyloid is imported into mitochondria remains uncertain.…”

Section: Trap1mentioning

confidence: 99%

Role of Mitochondrial Heat-shock Proteins and Immunophilins in Neuro Degenerative Diseases

Daneri-Becerra

Ciucci

Mazaira

et al. 2021

CDT

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Abstract:: Pathophysiologic conditions of neurodegenerative diseases are unquestionably related to protein misfolding. The accumulation of misfolded proteins into relatively ordered structures such as fibrillar intracellular and extracellular amyloids results in tissue lesions that lead to neuronal loss and brain damage. In these pathologies, the occurrence of protein aggregates suggests certain inefficient or insufficient cellular response of those molecular chaperones that should properly assist the folding of the client proteins. In this regard, all the experimental models for neurodegenerative diseases have demonstrated that the overexpression of molecular chaperones provide effective neuroprotection. A subset of these molecular chaperones corresponds to a group of proteins that exhibit peptidylprolyl isomerase enzymatic activity, the immunophilins. Most of the family members of the latter group were first described as responsible of the immunosuppressive response or they were reported as members of the chaperone complex associated with HSP90 in steroid receptor oligomers. In this article we review some aspects of the liaison between molecular chaperones and neurodegenerative diseases, in particular heat-shock proteins and immunophilins with demonstrated influence in the proper function of mitochondria. This article is intended to address a field that represents a yet critical unmet clinical need for the development of neuroprotective molecules focused on potentially novel molecular targets.

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TRAP1: A Metabolic Hub Linking Aging Pathophysiology to Mitochondrial S-Nitrosylation

Cited by 8 publications

References 38 publications

TRAP1 Shows Clinical Significance in the Early Diagnosis of Small Cell Lung Cancer

TRAP1 Shows Clinical Significance in the Early Diagnosis of Small Cell Lung Cancer

TRAP1 in Oxidative Stress and Neurodegeneration

Role of Mitochondrial Heat-shock Proteins and Immunophilins in Neuro Degenerative Diseases

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