Antonietta Franco

Antonietta Franco
Washington University in St. Louis | WUSTL , Wash U · Center for Pharmacogenomics

About

29
Publications
3,262
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707
Citations
Additional affiliations
August 2013 - October 2013
May 2013 - May 2016
August 2011 - September 2011
Imperial College London
Position
  • Student

Publications

Publications (29)
Article
Full-text available
Mitochondrial repair is essential to metabolic homeostasis. Outer mitochondrial membrane mitofusin (MFN) proteins orchestrate mitochondrial fusion that opposes mitochondrial degeneration caused by senescence. Depending upon physiological context, MFN2 can either mediate mitochondrial fusion or recruit cytosolic Parkin to initiate mitophagic elimina...
Article
Full-text available
Charcot-Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological activation of endogenous normal mitofusins overcame dominant inhibitory effects of CMT2A mutants in reprogrammed human patient motor neurons, reversing hallma...
Article
Mutations in the mitochondrial fusion protein mitofusin (MFN) 2 cause the chronic neurodegenerative condition Charcot-Marie-Tooth Disease type 2A (CMT2A), for which there is currently no treatment. Small molecule activators of MFN1 and MFN2 enhance mitochondrial fusion and offer promise as therapy for this condition, but prototype compounds have po...
Article
Full-text available
Aims The effects of GRK2 inhibition on myocardial metabolism in heart failure (HF) are unchartered. In this work, we evaluated the impact of pharmacological inhibition of GRK2 by a cyclic peptide, C7, on metabolic, biochemical, and functional phenotypes in experimental HF. Methods and results C7 was initially tested on adult mice ventricular myocy...
Article
Full-text available
Dynamic regulation of the mitochondrial network by mitofusins (MFNs) modulates energy production, cell survival, and many intracellular signaling events including calcium handling. However, the relative importance of specific mitochondrial functions and their dependence on MFNs vary greatly among cell types. Osteoclasts have many mitochondria, and...
Article
Mitofusin-2 (MFN2) is a mitochondrial outer-membrane protein that plays a pivotal role in mitochondrial dynamics in most tissues, yet mutations in MFN2, which cause Charcot-Marie-Tooth disease type 2A (CMT2A), primarily affect the nervous system. We generated a transgenic mouse model of CMT2A that developed severe early onset vision loss and neurol...
Article
Full-text available
The modern understanding of the G protein-coupled receptor kinase 2 has grown towards the definition of a stress protein, for its ability to rapidly compartmentalize within the cell in response to acute stimulation. Also, mitochondria can be regulated by GRK2 localization. We show that Ionizing Radiation (IR) exposure acutely damages mitochondria r...
Article
G-protein receptor kinases (GRKs) regulate adult hearts by modulating inotropic, chronotropic and hypertrophic signaling of 7-transmembrane spanning neurohormone receptors. GRK-mediated desensitization and downregulation of β-adrenergic receptors has been implicated in adult heart failure; GRKs are therefore a promising therapeutic target. However,...
Article
Full-text available
Mitofusins (MFNs) promote fusion-mediated mitochondrial content exchange and subcellular trafficking. Mutations in Mfn2 cause neurodegenerative Charcot-Marie-Tooth disease type 2A (CMT2A). We showed that MFN2 activity can be determined by Met376 and His380 interactions with Asp725 and Leu727 and controlled by PINK1 kinase-mediated phosphorylation o...
Article
Mitochondrial fusion and fission are critical to heart health; genetically interrupting either is rapidly lethal. To understand whether it is loss of, or the imbalance between, fusion and fission that underlies observed cardiac phenotypes, we engineered mice in which Mfn-mediated fusion and Drp1-mediated fission could be concomitantly abolished. Co...
Article
Full-text available
Mitochondria are dynamic organelles, remodeling and exchanging contents during cyclic fusion and fission. Genetic mutations of mitofusin (Mfn) 2 interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition, Charcot Marie Tooth disease type 2A (CMT2A). It has not been possible to directly modulate mitochondrial fusion, in par...
Article
Full-text available
GRK5 is a multifunctional protein that is able to move within the cell in response to various stimuli to regulate key intracellular signaling from receptor activation, on plasmamembrane, to gene transcription, in the nucleus. Thus, GRK5 is involved in the development and progression of several pathological conditions including cancer. Several repor...
Article
Full-text available
High-precision radiation therapy is a clinical approach that uses the targeted delivery of ionizing radiation, and the subsequent formation of reactive oxygen species (ROS) in high proliferative, radiation sensitive cancers. In particular, in thoracic cancer ratdiation treatments, can not avoid a certain amount of cardiac toxicity. Given the low pr...
Article
Full-text available
G protein coupled receptor kinase type 2 (GRK2) plays an important role in the development and maintenance of cardiac hypertrophy and heart failure even if its exact role is still unknown. In this study, we assessed the effect of GRK2 on the regulation of cardiac hypertrophy. In H9C2 cells, GRK2 overexpression increased atrial natriuretic factor (A...
Article
Full-text available
G protein coupled receptor kinase type 2 (GRK2) plays an important role in the development and maintenance of cardiac hypertrophy and heart failure even if its exact role is still unknown. In this study, we assessed the effect of GRK2 on the regulation of cardiac hypertrophy. In H9C2 cells, GRK2 overexpression increased atrial natriuretic factor (A...
Article
The natural process of aging determinates several cardiac modifications with increased susceptibility to heart diseases and ultimately converging on development of chronic heart failure as final stage. These changes mainly include left ventricular hypertrophy, diastolic dysfunction, valvular degeneration, increased cardiac fibrosis, increased preva...
Article
Full-text available
AIMS: Activation of Ca2+/Calmodulin protein kinase II (CaMKII) is an important step in signaling of cardiac hypertrophy. The molecular mechanisms by which CaMKII integrates with other pathways in the heart are incompletely understood. We hypothesize that CaMKII association with extracellular regulated kinase (ERK), promotes cardiac hypertrophy thr...
Article
Full-text available
GRK2 is an ubiquitous 80kd protein that interacts with several molecular partners in different cellular compartments. Recent studies have shown in endothelial cells that GRK2 localizes within the mitochondria, improves biogenesis and protects from ATP loss in response to ischemia/reperfusion. To evaluate cellular trafficking of GRK2 in isolated adu...
Article
Full-text available
Heart Failure (HF) is a complex disease characterized by progressive cardiac dilation and loss of ATP content needed to accomplish myocardial contractile function. GRK2 is a serine/threonine kinase that phosphorylates and binds receptors coupled to G proteins, such as β-adrenergic receptors (βAR) and it is involved in the pathophysiology of HF sinc...
Article
Full-text available
Cardiovascular diseases (CVD) include a heterogeneous group of multifactorial conditions and represent the major health problem in the western society. Many studies have evidenced that inter-individual variability affects the prognosis and the response to pharmacological treatment in patients with CVD. The identification of genetic markers to selec...
Article
The role of endothelial G protein-coupled receptor kinase 2 (GRK2) was investigated in mice with selective deletion of the kinase in the endothelium (Tie2-CRE/GRK2(fl/fl)). Aortas from Tie2-CRE/GRK2(fl/fl) presented functional and structural alterations as compared with control GRK2(fl/fl) mice. In particular, vasoconstriction was blunted to differ...
Article
eNOS is fundamental to regulate vascular functions such vasodilation, permeability and it has been demonstrated that overexpression of the Kinase of G protein coupled receptor 2 (GRK2) in endothelial cell (EC) reduces eNOS activity through AKT. However potential implication of GRK2 inhibition/removal from EC has not been explored yet. For this aim,...

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Project (1)
Project
This seven membrane receptor kinase appears to interact with other molecules in the cell, away from the plasmamembrane The mitochondrium is a preferential site of localization for this kinase. We want to investigate how GRK2 interacts with mitochondrial structure, fate and function, in physiology and in disease