The Mitochondrial HSP90 Paralog TRAP1: Structural Dynamics, Interactome, Role in Metabolic Regulation, and Inhibitors

Enhanced Expression of TRAP1 Protects Mitochondrial Function in Motor Neurons under Conditions of Oxidative Stress

(2022) Benjamin E. Clarke et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The mitochondrial chaperone TRAP1 regulates F-ATP synthase channel formation

(2022) Giuseppe Cannino et al.   CELL DEATH AND DIFFERENTIATION

TRAP1 regulates the response of colorectal cancer cells to hypoxia and inhibits ribosome biogenesis under conditions of oxygen deprivation

(2022) Giuseppina Bruno et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

The molecular chaperone TRAP1 in cancer: From the basics of biology to pharmacological targeting

(2021) Ionica Masgras et al.   SEMINARS IN CANCER BIOLOGY

TRAP1 in Oxidative Stress and Neurodegeneration

(2021) Inês Ramos Rego et al.   Antioxidants

TRAP1 inhibits MIC60 ubiquitination to mitigate the injury of cardiomyocytes and protect mitochondria in extracellular acidosis

(2021) Lingxiao Zhang et al.   Cell Death Discovery

The mitochondrial HSP90 paralog TRAP1 forms an OXPHOS-regulated tetramer and is involved in mitochondrial metabolic homeostasis

(2020) Abhinav Joshi et al.   BMC BIOLOGY

Dual Binding to Orthosteric and Allosteric Sites Enhances the Anticancer Activity of a TRAP1-Targeting Drug

(2020) Sung Hu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Honokiol bis-dichloroacetate is a selective allosteric inhibitor of the mitochondrial chaperone TRAP1

(2020) Carlos Sanchez-Martin et al.   ANTIOXIDANTS & REDOX SIGNALING

Rational Design of Allosteric and Selective Inhibitors of the Molecular Chaperone TRAP1

(2020) Carlos Sanchez-Martin et al.   Cell Reports

Succinate Supplement Elicited “Pseudohypoxia” Condition to Promote Proliferation, Migration, and Osteogenesis of Periodontal Ligament Cells

(2020) Huimin Mao et al.   Stem Cells International

Inhibition of HDAC1/2 Along with TRAP1 Causes Synthetic Lethality in Glioblastoma Model Systems

(2020) Trang T. T. Nguyen et al.   Cells

Take Advantage of Glutamine Anaplerosis, the Kernel of the Metabolic Rewiring in Malignant Gliomas

(2020) Filipa Martins et al.   Biomolecules

Mitochondrial Dysfunction and Mitophagy in Parkinson’s Disease: From Mechanism to Therapy

(2020) Ana Belen Malpartida et al.   TRENDS IN BIOCHEMICAL SCIENCES

Interaction of germline variants in a family with a history of early‐onset clear cell renal cell carcinoma

(2019) Emmanuelle Nicolas et al.   Molecular Genetics & Genomic Medicine

Hypoxia/pseudohypoxia‐mediated activation of hypoxia‐inducible factor‐1α in cancer

(2019) Yoshihiro Hayashi et al.   CANCER SCIENCE

Interplay between TRAP1 and sirtuin-3 modulates mitochondrial respiration and oxidative stress to maintain stemness of glioma stem cells

(2019) Hye-Kyung Park et al.   CANCER RESEARCH

Impact of Mutations on NPAC Structural Dynamics: Mechanistic Insights from MD Simulations

(2019) Marco Montefiori et al.   Journal of Chemical Information and Modeling

Hsp90 quaternary structures and the chaperone cycle: highly flexible dimeric and oligomeric structures and their regulation by co-chaperones

(2018) Cyrille Garnier et al.   Current Proteomics

Calcium binding to a remote site can replace magnesium as cofactor for mitochondrial Hsp90 (TRAP1) ATPase activity

(2018) Daniel Elnatan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Structural Asymmetry of Mitochondrial Hsp90 (Trap1) Determines Fine Tuning of Functional Dynamics

(2018) Elisabetta Moroni et al.   Journal of Chemical Theory and Computation

Dancing with the Diva: Hsp90–Client Interactions

(2018) Martina Radli et al.   JOURNAL OF MOLECULAR BIOLOGY

Overexpression of the mitochondrial chaperone tumor necrosis factor receptor‑associated protein 1 is associated with the poor prognosis of patients with colorectal cancer

(2018) Chang Gao et al.   Oncology Letters

HSP90 inhibitors disrupt a transient HSP90-HSF1 interaction and identify a noncanonical model of HSP90-mediated HSF1 regulation

(2018) Toshiki Kijima et al.   Scientific Reports

Mitochondria are physiologically maintained at close to 50 °C

(2018) Dominique Chrétien et al.   PLOS BIOLOGY

TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria

(2017) Jun-Feng Chen et al.   FASEB JOURNAL

Paralog Specificity Determines Subcellular Distribution, Action Mechanism, and Anticancer Activity of TRAP1 Inhibitors

(2017) Hye-Kyung Park et al.   JOURNAL OF MEDICINAL CHEMISTRY

The HSP90 chaperone machinery

(2017) Florian H. Schopf et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Mitochondrial matrix chaperone and c-myc inhibition causes enhanced lethality in glioblastoma

(2017) Chiaki Tsuge Ishida et al.   Oncotarget

A Mitochondrial-targeted purine-based HSP90 antagonist for leukemia therapy

(2017) Kelly G. Bryant et al.   Oncotarget

Cytosolic Hsp90α and its mitochondrial isoform Trap1 are differentially required in a breast cancer model

(2017) Evangelia Vartholomaiou et al.   Oncotarget

Symmetry broken and rebroken during the ATP hydrolysis cycle of the mitochondrial Hsp90 TRAP1

(2017) Daniel Elnatan et al.   eLife

Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis

(2016) Laszlo Tretter et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS

Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors

(2016) Gao Zhang et al.   JOURNAL OF CLINICAL INVESTIGATION

Mitochondrial Hsp90 is a ligand-activated molecular chaperone coupling ATP binding to dimer closure through a coiled-coil intermediate

(2016) Nuri Sung et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Holdase activity of secreted Hsp70 masks amyloid-β42 neurotoxicity inDrosophila

(2016) Pedro Fernandez-Funez et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Metabolic reprogramming identifies the most aggressive lesions at early phases of hepatic carcinogenesis

(2016) Marta Anna Kowalik et al.   Oncotarget

TRAP1 Provides Protection Against Myocardial Ischemia-Reperfusion Injury by Ameliorating Mitochondrial Dysfunction

(2015) Peng Zhang et al.   CELLULAR PHYSIOLOGY AND BIOCHEMISTRY

Regulation and function of the human HSP90AA1 gene

(2015) Abbey D. Zuehlke et al.   GENE

Development of a Mitochondria-Targeted Hsp90 Inhibitor Based on the Crystal Structures of Human TRAP1

(2015) Changwook Lee et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Hurt, tired and queasy: Specific variants in the ATPase domain of the TRAP1 mitochondrial chaperone are associated with common, chronic “functional” symptomatology including pain, fatigue and gastrointestinal dysmotility

(2015) Richard G. Boles et al.   MITOCHONDRION

Human Hsp70 Disaggregase Reverses Parkinson’s-Linked α-Synuclein Amyloid Fibrils

(2015) Xuechao Gao et al.   MOLECULAR CELL

Impact of holdase chaperones Skp and SurA on the folding of β-barrel outer-membrane proteins

(2015) Johannes Thoma et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Overexpression of tumor necrosis factor receptor-associated protein 1 (TRAP1) are associated with poor prognosis of epithelial ovarian cancer

(2015) Qingjie Lv et al.   TUMOR BIOLOGY

Impact of holdase chaperones Skp and SurA on the folding of β-barrel outer-membrane proteins

(2015) Johannes Thoma et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Aberrantly upregulated TRAP1 is required for tumorigenesis of breast cancer

(2015) Bo Zhang et al.   Oncotarget

Lipophilic Triphenylphosphonium Cations Inhibit Mitochondrial Electron Transport Chain and Induce Mitochondrial Proton Leak

(2015) Jan Trnka et al.   PLoS One

Client Proteins and Small Molecule Inhibitors Display Distinct Binding Preferences for Constitutive and Stress-Induced HSP90 Isoforms and Their Conformationally Restricted Mutants

(2015) Thomas L. Prince et al.   PLoS One

TRAP1 Shows Clinical Significance and Promotes Cellular Migration and Invasion through STAT3/MMP2 Pathway in Human Esophageal Squamous Cell Cancer

(2014) Yunwei Ou et al.   Journal of Genetics and Genomics

Expression of TRAP1 Predicts Poor Survival of Malignant Glioma Patients

(2014) Shuai Li et al.   JOURNAL OF MOLECULAR NEUROSCIENCE

Homozygous TRAP1 sequence variant in a child with Leigh syndrome and normal kidneys

(2014) Stephanie J. Skinner et al.   KIDNEY INTERNATIONAL

Structural Asymmetry in the Closed State of Mitochondrial Hsp90 (TRAP1) Supports a Two-Step ATP Hydrolysis Mechanism

(2014) Laura A. Lavery et al.   MOLECULAR CELL

Mitochondrial oxidative phosphorylation TRAP(1)ped in tumor cells

(2014) Andrea Rasola et al.   TRENDS IN CELL BIOLOGY

Up-regulation of mitochondrial chaperone TRAP1 in ulcerative colitis associated colorectal cancer

(2014) Ru Chen   WORLD JOURNAL OF GASTROENTEROLOGY

Deletion of the Mitochondrial Chaperone TRAP-1 Uncovers Global Reprogramming of Metabolic Networks

(2014) Sofia Lisanti et al.   Cell Reports

A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity

(2014) James R Partridge et al.   eLife

Molecular Chaperone Functions in Protein Folding and Proteostasis

(2013) Yujin E. Kim et al.   Annual Review of Biochemistry

The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase

(2013) Marco Sciacovelli et al.   Cell Metabolism

TRAP1 rescues PINK1 loss-of-function phenotypes

(2013) Li Zhang et al.   HUMAN MOLECULAR GENETICS

Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association

(2013) Pawaree Saisawat et al.   KIDNEY INTERNATIONAL

Proteomic Differences Between Hepatocellular Carcinoma and Nontumorous Liver Tissue Investigated by a Combined Gel-based and Label-free Quantitative Proteomics Study

(2013) Dominik A. Megger et al.   MOLECULAR & CELLULAR PROTEOMICS

Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis

(2013) S. Yoshida et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Drosophila Trap1 protects against mitochondrial dysfunction in a PINK1/parkin model of Parkinson’s disease

(2013) A C Costa et al.   Cell Death & Disease

Landscape of the mitochondrial Hsp90 metabolome in tumours

(2013) Young Chan Chae et al.   Nature Communications

TRAP1 regulation of mitochondrial life or death decision in cancer cells and mitochondria-targeted TRAP1 inhibitors

(2012) Byoung-Heon Kang   BMB Reports

Control of Tumor Bioenergetics and Survival Stress Signaling by Mitochondrial HSP90s

(2012) Young Chan Chae et al.   CANCER CELL

TRAP1 Controls Mitochondrial Fusion/Fission Balance through Drp1 and Mff Expression

(2012) Hironori Takamura et al.   PLoS One

Charged linker sequence modulates eukaryotic heat shock protein 90 (Hsp90) chaperone activity

(2012) S. Tsutsumi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Correlation between mitochondrial TRAP-1 expression and lymph node metastasis in colorectal cancer

(2012) Jing-Yan Gao   WORLD JOURNAL OF GASTROENTEROLOGY

The Mitochondrial Chaperone Protein TRAP1 Mitigates α-Synuclein Toxicity

(2012) Erin K. Butler et al.   PLoS Genetics

GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum

(2011) Michal Marzec et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Molecular chaperones in protein folding and proteostasis

(2011) F. Ulrich Hartl et al.   NATURE

The Hexameric Structures of Human Heat Shock Protein 90

(2011) Cheng-Chung Lee et al.   PLoS One

Preclinical Characterization of Mitochondria-Targeted Small Molecule Hsp90 Inhibitors, Gamitrinibs, in Advanced Prostate Cancer

(2010) B. H. Kang et al.   CLINICAL CANCER RESEARCH

Mitochondrial chaperone tumour necrosis factor receptor-associated protein 1 protects cardiomyocytes from hypoxic injury by regulating mitochondrial permeability transition pore opening

(2010) Fei Xiang et al.   FEBS Journal

Biochemical and Biophysical Characterization of the Mg2+-induced 90-kDa Heat Shock Protein Oligomers

(2010) Laura Moullintraffort et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Heat Shock Response: Life on the Verge of Death

(2010) Klaus Richter et al.   MOLECULAR CELL

HSP90 at the hub of protein homeostasis: emerging mechanistic insights

(2010) Mikko Taipale et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Glutamine addiction: a new therapeutic target in cancer

(2010) David R. Wise et al.   TRENDS IN BIOCHEMICAL SCIENCES

Cytoprotective Mitochondrial Chaperone TRAP-1 As a Novel Molecular Target in Localized and Metastatic Prostate Cancer

(2009) Irwin Leav et al.   AMERICAN JOURNAL OF PATHOLOGY

Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3

(2009) Martin Gamerdinger et al.   EMBO JOURNAL

Combinatorial drug design targeting multiple cancer signaling networks controlled by mitochondrial Hsp90

(2009) Byoung Heon Kang et al.   JOURNAL OF CLINICAL INVESTIGATION

BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90

(2009) K. Lundgren et al.   MOLECULAR CANCER THERAPEUTICS

Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation

(2009) M. G. Vander Heiden et al.   SCIENCE

Targeting Mitochondria

(2008) Adam T. Hoye et al.   ACCOUNTS OF CHEMICAL RESEARCH

Cancer Cell Metabolism: Warburg and Beyond

(2008) Peggy P. Hsu et al.   CELL

The ATPase Cycle of the Mitochondrial Hsp90 Analog Trap1

(2008) Adriane Leskovar et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Overexpression of Mitochondrial Hsp70/Hsp75 in Rat Brain Protects Mitochondria, Reduces Oxidative Stress, and Protects from Focal Ischemia

(2008) Lijun Xu et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM