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

Targeting the mitochondrial chaperone TRAP1: strategies and therapeutic perspectives

(2021) Stefano A. Serapian et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia

(2021) Claudio Laquatra et al.   Cell Death & Disease

S-nitrosylation affects TRAP1 structure and ATPase activity and modulates cell response to apoptotic stimuli

(2020) Fiorella Faienza et al.   BIOCHEMICAL PHARMACOLOGY

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

(2020) Abhinav Joshi et al.   BMC BIOLOGY

Defects in long chain 3‐hydroxy acyl‐CoA dehydrogenase lead to hepatocellular carcinoma: A novel etiology of hepatocellular carcinoma

(2020) Tripti Khare et al.   INTERNATIONAL JOURNAL OF CANCER

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

HSF1 is required for induction of mitochondrial chaperones during the mitochondrial unfolded protein response

(2020) Arpit Katiyar et al.   FEBS Open Bio

TRAP1 attenuates H9C2 myocardial cell injury induced by extracellular acidification via the inhibition of MPTP opening

(2020) Lingxiao Zhang et al.   INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE

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

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

Dynamically Shaping Chaperones. Allosteric Modulators of HSP90 Family as Regulatory Tools of Cell Metabolism in Neoplastic Progression

(2020) Carlos Sanchez-Martin et al.   Frontiers in Oncology

Cryo-EM structure of the entire mammalian F-type ATP synthase

(2020) Gergely Pinke et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

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

F‐ ATP Synthase and the Permeability Transition Pore: Fewer doubts, more certainties

(2019) Michela Carraro et al.   FEBS LETTERS

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

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

A Novel MYCN-Specific Antigene Oligonucleotide Deregulates Mitochondria and Inhibits Tumor Growth in MYCN-Amplified Neuroblastoma

(2019) Luca Montemurro et al.   CANCER RESEARCH

Purified F-ATP synthase forms a Ca2+-dependent high-conductance channel matching the mitochondrial permeability transition pore

(2019) Andrea Urbani et al.   Nature Communications

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

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

Mitochondria are physiologically maintained at close to 50 °C

(2018) Dominique Chrétien et al.   PLOS BIOLOGY

Metabolic Plasticity of Tumor Cell Mitochondria

(2018) Giuseppe Cannino et al.   Frontiers in Oncology

PRC2 loss induces chemoresistance by repressing apoptosis in T cell acute lymphoblastic leukemia

(2018) Ingrid M. Ariës et al.   JOURNAL OF EXPERIMENTAL MEDICINE

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

Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells

(2017) Farhan Basit et al.   Cell Death & Disease

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

Absence of Neurofibromin Induces an Oncogenic Metabolic Switch via Mitochondrial ERK-Mediated Phosphorylation of the Chaperone TRAP1

(2017) Ionica Masgras et al.   Cell Reports

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

(2017) Daniel Elnatan et al.   eLife

The Chaperone TRAP1 As a Modulator of the Mitochondrial Adaptations in Cancer Cells

(2017) Ionica Masgras et al.   Frontiers in Oncology

S -nitrosylation of the Mitochondrial Chaperone TRAP1 Sensitizes Hepatocellular Carcinoma Cells to Inhibitors of Succinate Dehydrogenase

(2016) Salvatore Rizza et al.   CANCER RESEARCH

Mitochondria and Cancer

(2016) Sejal Vyas et al.   CELL

TRAP1 regulates stemness through Wnt/β-catenin pathway in human colorectal carcinoma

(2016) Giacomo Lettini et al.   CELL DEATH AND DIFFERENTIATION

Oxidative metabolism drives inflammation-induced platinum resistance in human ovarian cancer

(2016) D S Matassa et al.   CELL DEATH AND DIFFERENTIATION

The Emerging Hallmarks of Cancer Metabolism

(2016) Natalya N. Pavlova et al.   Cell Metabolism

Transgenic Expression of the Mitochondrial Chaperone TNFR-associated Protein 1 (TRAP1) Accelerates Prostate Cancer Development

(2016) Sofia Lisanti et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors

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

A Novel In Vitro CypD-Mediated p53 Aggregation Assay Suggests a Model for Mitochondrial Permeability Transition by Chaperone Systems

(2016) Ivan Lebedev et al.   JOURNAL OF MOLECULAR BIOLOGY

Downregulation of TRAP1 sensitizes glioblastoma cells to temozolomide chemotherapy through regulating metabolic reprogramming

(2016) Jianing Wu et al.   NEUROREPORT

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

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

Overexpression of mitochondrial Hsp75 protects neural stem cells against microglia-derived soluble factor-induced neurotoxicity by regulating mitochondrial permeability transition pore opening in vitro

(2015) YAN WANG et al.   INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE

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

The Mitochondrial Permeability Transition Pore: Channel Formation by F-ATP Synthase, Integration in Signal Transduction, and Role in Pathophysiology

(2015) Paolo Bernardi et al.   PHYSIOLOGICAL REVIEWS

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

Aberrantly upregulated TRAP1 is required for tumorigenesis of breast cancer

(2015) Bo Zhang et al.   Oncotarget

Targeting TRAP1 as a downstream effector of BRAF cytoprotective pathway: a novel strategy for human BRAF-driven colorectal carcinoma

(2015) Valentina Condelli et al.   Oncotarget

Inhibition of succinate dehydrogenase by the mitochondrial chaperone TRAP1 has anti-oxidant and anti-apoptotic effects on tumor cells

(2015) Giulia Guzzo et al.   Oncotarget

Overexpression of tumor necrosis factor receptor-associated protein 1 (TRAP1), leads to mitochondrial aberrations in mouse fibroblast NIH/3T3 cells

(2014) Chang-Nim Im et al.   BMB Reports

The mitochondrial permeability transition pore and its adaptive responses in tumor cells

(2014) Andrea Rasola et al.   CELL CALCIUM

Suppression of tumor necrosis factor receptor-associated protein 1 expression induces inhibition of cell proliferation and tumor growth in human esophageal cancer cells

(2014) Xin Tian et al.   FEBS Journal

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

TRAP1 Regulates Proliferation, Mitochondrial Function, and Has Prognostic Significance in NSCLC

(2014) Jackeline Agorreta et al.   MOLECULAR CANCER RESEARCH

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

PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies

(2014) Thomas De Raedt et al.   NATURE

PRC2 loss amplifies Ras signaling in cancer

(2014) Annika Baude et al.   NATURE GENETICS

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

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

Metabolic stress regulates cytoskeletal dynamics and metastasis of cancer cells

(2013) M. Cecilia Caino et al.   JOURNAL OF CLINICAL INVESTIGATION

HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations

(2013) Gregg L. Semenza   JOURNAL OF CLINICAL INVESTIGATION

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

Rare insights into cancer biology

(2013) J Adam et al.   ONCOGENE

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

Control of Tumor Bioenergetics and Survival Stress Signaling by Mitochondrial HSP90s

(2012) Young Chan Chae et al.   CANCER CELL

MYC on the Path to Cancer

(2012) Chi V. Dang   CELL

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

HSP75 protects against cardiac hypertrophy and fibrosis

(2011) Yan Zhang et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

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

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

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

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

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