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Last update 08 May 2025

TRAP1

Last update 08 May 2025

Basic Info

Synonyms

Heat shock protein 75 kDa, mitochondrial, HSP 75, HSP75

+ [7]

Introduction

Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA.

Drugs associated with TRAP1

dual HSP90/TRAP1 inhibitors (Plex Pharma)

Target

HSP90 x TRAP1

Mechanism

HSP90 inhibitors [+1]

Active Org.

Plex Pharmaceuticals, Inc.

Originator Org.

Plex Pharmaceuticals, Inc.

Active Indication

Brain metastases [+2]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ACU-D3

Target

TRAP1

Mechanism

TRAP1 antagonists

Active Org.

Accuitis, Inc.

Originator Org.

Accuitis, Inc.

Active Indication

Melanoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SH-491

Target

CTSK x MMP9 x TRAP1

Mechanism

CTSK inhibitors [+2]

Active Org.

East China Normal University

Originator Org.

East China Normal University

Active Indication

Osteoporosis

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TRAP1

100 Translational Medicine associated with TRAP1

0 Patents (Medical) associated with TRAP1

955

Literatures (Medical) associated with TRAP1

31 Dec 2025·Animal Cells and Systems

TRAP1 functions in the morphogenesis of the embryonic kidney

Article

Author: Kim, Ha Eun ; Kwon, Taejoon ; Sim, Hyo Jung ; Park, Tae Joo

TNF receptor-associated protein1 (TRAP1) is a mitochondrial molecular chaperon with high homology with a cytosolic chaperon HSP90. It has been shown that TRAP1 functions as an inhibitor for apoptosis by preventing cytochrome-c release from mitochondria. In addition, TRAP1 seems to play critical roles in metabolic processes for energy production, such as glycolysis and β-oxidation. It has also been reported that TRAP1 is a direct target of PTEN-induced kinase 1 (PINK1) and may be a cause of Parkinson's disease (PD) in humans. Although the biochemical functions of TRAP1 are under intense study for the physiology and treatment of various cancers, its roles in vertebrate development have not been reported. This study shows that Xenopus TRAP1 is strongly expressed in the developing muscle, kidney, and brain tissues. Perturbation of TRAP1 function by treating TRAP1 inhibiter GTPP or microinjection of antisense-morpholino oligo (MO) caused mild defects in striated muscle fiber formation. Furthermore, the looping patterns of developing kidney tubules were perturbed, indicating that TRAP1 function is necessary for proper kidney development.

01 Jul 2025·Drug Resistance Updates

Targeting TRAP1-dependent metabolic reprogramming to overcome doxorubicin resistance in quiescent breast cancer

Article

Author: Xu, Jianhua ; Huang, Yingying ; Huang, Ruyi ; Ye, Shengnan ; Saleem, Muhammad Zubair ; Chen, Zhe-Sheng ; Ke, Zun-Fu ; Fan, Yinjuan ; Gao, Miao ; Guo, Xin ; Liu, Yang

AIMSTRAP1 is involved in metabolic reprogramming and promotes drug resistance. We aimed to explore whether a novel HSP90 inhibitor, C210, overcomes doxorubicin (DOX) resistance of quiescent breast cancer cells by targeting TRAP1.METHODSBreast cancer cells were induced to quiescence by hypoxia and low glucose. The relationship of cell metabolism with HSP90 and TRAP1 was investigated by Western blotting, ECAR, OCR, mitochondrial complex activity, and proteomic analysis. The targets of C210 and their functions were analyzed by SPR and immunoprecipitation. The antitumor effect in vivo was investigated with mouse tumor model.RESULTSIn hypoxia and glucose deprivation, breast cancer cells exhibited elevated TRAP1 and an OXPHOS-enhanced quiescent phenotype. These cells were highly resistant to DOX but more sensitive to C210. C210 disrupted TRAP1's interaction with OXPHOS-associated client proteins, prompting proteasome-dependent degradation of these proteins, thereby reducing OCR, mitochondrial ATP production and resulting in selective elimination of the quiescent cancer cells by inducing mitochondrial apoptosis which could be reversed by exogenous ATP. Moreover, C210 targeted glycolytic, amino acid, and β-oxidation-associated proteome. C210 demonstrated promising in vivo anticancer efficacy which was particularly related to OXPHOS inhibition.CONCLUSIONSC210 eliminates DOX-resistant quiescent breast cancer cells by targeting TRAP1-dependent bioenergetics.

09 Apr 2025·mBio

The HOPS and vCLAMP protein Vam6 connects polyphosphate with mitochondrial function and oxidative stress resistance in Cryptococcus neoformans

Article

Author: Kronstad, James W. ; Lagace, Melissa ; Bhalla, Kabir ; Lee, Christopher W. J. ; Jung, Won Hee ; Hu, Guanggan ; Sánchez-León, Eddy

ABSTRACTCryptococcus neoformans is considered one of the most dangerous fungal threats to human health, and the World Health Organization recently ranked it in the critical priority group for perceived public health importance. Proliferation of C. neoformans within mammalian hosts is supported by its ability to overcome nutritional limitations and endure stress conditions induced by the host immune response. Previously, we reported that the Vam6/Vps39/TRAP1-domain protein Vam6 was crucial for vacuolar morphology, iron acquisition, and virulence. However, the molecular mechanisms underlying the pleiotropic phenotypes resulting from loss of Vam6 remain poorly understood. In this study, we determined that Vam6 has roles in the HOPS complex for endomembrane trafficking to the vacuole and in the vCLAMP membrane contact site between the vacuole and mitochondria. Importantly, both of these roles regulate polyphosphate (polyP) metabolism, as demonstrated by a defect in trafficking of the VTC complex subunit Vtc2 for polyphosphate synthesis and by an influence on mitochondrial functions. In the latter case, Vam6 was required for polyP accumulation in response to electron transport chain inhibition and for overcoming oxidative stress. Overall, this work establishes connections between endomembrane trafficking, mitochondrial functions, and polyP homeostasis in C. neoformans . IMPORTANCE A detailed understanding of stress resistance by fungal pathogens of humans may provide new opportunities to improve antifungal therapy and combat life-threatening diseases. Here, we used a vam6 deletion mutant to investigate the role of the homotypic fusion and vacuole protein sorting (HOPS) complex in mitochondrial functions and polyphosphate homeostasis in Cryptococcus neoformans , an important fungal pathogen of immunocompromised people including those suffering from HIV/AIDS. Specifically, we made use of mutants defective in late endocytic trafficking steps to establish connections to oxidative stress and membrane trafficking with mitochondria. In particular, we found that mutants lacking the Vam6 protein had altered mitochondrial function, and that the mutants were perturbed for additional mitochondria and vacuole-related phenotypes (e.g., membrane composition, polyphosphate accumulation, and drug sensitivity). Overall, our study establishes connections between endomembrane trafficking components, mitochondrial functions, and polyphosphate homeostasis in an important fungal pathogen of humans.

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TRAP1

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