Mining the gut microbiome for novel mitochondrial therapeutics: A strategic Presentation by Pr Anurag Agrawal
During the 6th World Congress on Targeting Mitochondria, Pr Anurag Agrawal from CSIR Institute of Genomics and Integrative Biology, India will discuss about a strategic topic: "Mining the gut microbiome for novel mitochondrial therapeutics".
He will highlight the following points:
- Mapping the gut microbial reactome to mitochondrial metabolism
- The strange case of PQQ
- Effects of common gut metabolites on mitochondrial function
If you would like to access to the complete program of Targeting Mitochondria 2015: www.targeting-mitochondria.com
Pr Luis Vitetta, from Sydney University will talk about Reactive oxygen species and their lifelong regulation of the metabolome
The production of reactive oxygen species and reactive nitrogen species has long been proposed as leading to the random deleterious modification of macromolecules with an associated progressive development of age associated systemic disease. Superoxide anion (and hydrogen peroxide) and nitric oxide (and peroxynitrite) constitute regulated prooxidant second messenger systems, with specific sub-cellular locales of production and are essential for normal metabolome and physiological function.
Pr Vitetta's team has posited that the formation of superoxide anion/hydrogen peroxide and nitric oxide do not conditionally lead to random macromolecular damage. Under normal physiological conditions their production is actually regulated that is very much consistent with their second messenger roles. The role of these second messengers in the regulation of the metabolome is discussed in terms of radical formation as an essential contributor to the physiologically normal regulation of sub-cellular bioenergy systems; proteolysis regulation; transcription activation; enzyme activation; mitochondrial DNA changes; redox regulation of metabolism and cell differentiation.
Furthermore the concept that orally administered small molecule antioxidant therapy to abrogate free radical activity is a chimera. Hence as such they consider that free radicals are not a major overwhelming player in the development of the chronic diseases or the aging process.
You can know more about this study by joining Targeting Mitochondria World Congress.
For more information: www.targeting-mitochondria.com
Pr. Neuzil's talk to prerequisite for tumor initiation
During the 6th World Congress on Targeting Mitochondria, Pr. Neuzil will present the recent studies related to the acquisition of mitochondrial DNA by cancer cells devoid of mitochondrial genome.
According to him, "we have recently shown that cancer cells devoid of mitochondrial (mt) DNA form syngeneic tumours with a delay, and the tumour cells contain the host mtDNA. Here, we studied what happens during the lag phase before a tumour starts to grow. We show that several days after grafting, tumour cells start to acquire mtDNA from host cells, and its level increases until the tumour appears and starts to progress. This is accompanied by mtDNA replication and transcription, which promotes retrograde signaling to the nucleus, assembly of mitochondrial complexes and recovery of respiration. We conclude that cancer cells devoid of mtDNA ought to recover oxidative phosphorylation to a threshold level, which is a prerequisite for the cells to initiate tumour formation and growth."
If you are interested to know more about the results of this study, don't hesitate to join Targeting Mitochondria World Congress 2015.
For more information: www.targeting-mitochondria.com
Dr Koopman will present his researchs about live-cell quantification of mitochondrial readouts
Dr Werner Koopman, from Radboud University Medical Center, Netherlands will give a strategic presentation about life cell quantification of mitochondrial readouts.
His research aims to quantitatively understand the molecular connection between mitochondrial metabolism and (ultra)structure with particular attention to redox signaling and biomolecule diffusion. To this end, they study primary cells from mitochondrial disease patients, inhibitor-treated cells, a knockout mouse model of mitochondrial complex I (CI) deficiency and cancer cell lines to gain insight into the (tissue-specific) consequences and/or adaptation programs triggered by mitochondrial dysfunction. Given the tight integration of mitochondrial and cellular metabolism, the above aims are primarily addressed in living cell systems.
As a key technology, protein-based and chemical fluorescent reporter molecules are introduced in the cells and their signals are quantified using life cell microscopy, image processing/quantification and data mining. Protein diffusion is studied by combining photobleaching strategies, single-molecule spectroscopy and in silico techniques. In primary fibroblasts from Leigh Syndrome (LS) patients, isolated CI deficiency is associated with mitochondrial morpho-functional changes and increased reactive oxygen species (ROS) levels.
Empirical evidence suggests these aberrations might constitute linked therapeutic targets for small chemical molecules. However, the latter generally induce multiple subtle effects, meaning that in vitro potency analysis or single-parameter high-throughput cell screening are of limited use to identify these molecules.
If you are interested to know more about the results of this study, don't hesitate to join Targeting Mitochondria World Congress 2015.
For more information: www.targeting-mitochondria.com
Targeting energy producing metabolic pathways for cancer therapy
Dr Vladimir Gogvadze, from Karolinska Institutet in Sweden is a special in the role of mitochondria in cancer field.
The scientific committee of the World Mitochondria Society is honoured to welcoming Dr Gogvadze during Targeting Mitochondria World Congress which will be held at Ritz Carlton, from October 28 to 30.
The majority of cancers demonstrate various tumor-specific metabolic aberrations, such as increased glycolysis even under aerobic conditions (Warburg effect), whereas mitochondrial metabolic activity and their contribution to cellular energy production are restrained. The “glycolytic shift” in tumor cells offered a rationale for therapeutic strategies aimed at selective inhibition of the glycolytic pathway. This approach could be most useful in cells with mitochondrial defects, or under hypoxic conditions, when the mitochondrial contribution to cellular bioenergetics is minimal.
Dr Targeting Mitochondria World Congress, Dr Gogvadze will present the recent studies related to mitochondria & cancer.
For more information: www.targeting-mitochondria.com
Dr Das will present the recent advances on the role of mitochondria in RNA interference by miRNA activity
Dr Samarjit Das, from John Hopkins Unviersity, USA will give a strategic presentation about Mitochondrial microRNA, “MitomiR”: A new Player in Heart Failure.
According to Dr Das: "The goal of this project is to explore the novel concept that microRNA (miRNA) can regulate mitochondrial biology of the heart, and thereby affect myocardial disease development and progression. The field of miRNA biology has exploded recently, with many studies demonstrating that small non-coding RNA (miRNA) can repress the expression of target genes by post-transcriptional regulation and play a major role in many physiologic and pathologic processes. Several groups suggested that miRNA exist in mitochondria, but we were the first to show that miRNA exist in heart mitochondria and are functionally important."
If you are interested to know more about the results of this study, don't hesitate to join Targeting Mitochondria World Congress 2015.
For more information: www.targeting-mitochondria.com
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The scientific Committee of World Mitochondria Society published the program of the 6th World Congress on Targeting Mitochondria
On behalf of Scientific Committee of Targeting Mitochondria World Congress 2015, we are pleased to inform you about the publication of the program for the 6th World Congress on Targeting Mitochondria, which will be held at Hotel Ritz, Berlin from October 28 to 30, 2015.
To access to the agenda of Targeting Mitochondria 2015, please click here.
We remind you that you have un til September 30 to submit your abstract for poster presentation.
For more information: www.targeting-mitochondria.com
PSC-based drug discovery of mitochondrial disorders: Neural cells from patient-derived iPSCs as a novel system for drug discovery of mtDNA disorders
During Targeting Mitochondria 2015, Dr. Alessandro Prigione, from the Max Delbrück Center (MDC) of Berlin, will discuss how to develop novel drug discovery pipelines for mitochondrial DNA (mtDNA) disorders using induced pluripotent stem cells (iPSCs). Viable neural model systems of mtDNA brain disease are lacking due to the challenges of engineering mtDNA, thus hindering the search for therapeutic options. Here, we demonstrate that iPSC-derived neural cells may maintain the parental mtDNA profile and exhibit mitochondrial-based metabolism. Using this system, neural-specific dysfunctions due to homoplasmic mtDNA mutations could be identified. We therefore propose iPSC-derived neural cells as a novel model system for the establishment of personalized phenotypic drug discovery for untreatable mtDNA disorders affecting the nervous system.
For more information about Targeting Mitochondria World Congress: www.targeting-mitochondria.com
Treating cancer like an infectious disease: A strategy presented by Dr Rebecca Lamb during WMS Congress
During the 6th World Congress on Targeting Mitochondria scheduled from October 28 to 30 in Berlin, Dr Rebecca Lamb from the University of Manchester, UK will give a strategic presentation about Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease.
Dr Lamb and her team proposes a new strategy for the treatment of cancer, via the selective targeting of cancer stem cells (CSCs) responsible for tumour-initiation, progression, treatment resistance and disease recurrence. They utilized CSC activity as a global phenotypic characteristic of multiple tumour types, to provide a mutation-independent approach to cancer therapy, effectively treating cancer as a single disease of “stemness”.
If you would like to know more about the presentation from Dr Lamb, don't hesitate to register for Targeting Mitochondria World Congress.
More information on www.targeting-mitochondria.com
The central role of mitochondrial dysfunction in brain and other tissues pathophysiology evaluated in vivo presented by Prof. Avraham Mayevsky
During the Workshop organized on October 28, 2015, Prof. Avraham Mayevsky from Faculty of Life-Sciences and the Multidisciplinary Brain Research Center, Israel will present The central role of mitochondrial dysfunction in brain and other tissues pathophysiology evaluated in vivo.
He will talk about :
- Historical Overview – The 60 years legacy of Prof. Britton Chance.
- Brain and Tissue Energy Metabolism and Mitochondrial Function.
- Why and how to Monitor Mitochondrial NADH redox state in vivo.
- Multiparametric monitoring of NADH together with other tissue physiological activities.
- Responses of brain and other tissues to various perturbations in Animal Models.
- Monitoring of Mitochondrial NADH and microcirculatory blood flow and oxygenation in patients
Pictures and moments of Targeting Mitochondria World Congress 2014
We are very pleased to share with you a few pictures of the 5th Congress of Targeting Mitochondria 2014, which was held on October 29 to 31, 2014, at Hotel Ritz Carlton, Berlin.
We hope these picture will remind you of the best times of the Congress.
To access to the pictures gallery, please click here.
The Abstracts book of Targeting Mitochondria 2014 is now available in PDF version
All abstracts accepted by the Scientific Committee of Targeting Mitochondria 2014 are published in the abstracts book of the congress.
The abstracts book contains abstracts of major speakers, short oral presentations and posters presentations (186 pages).
You can order this Abstracts Book in PDF Format by clicking here.
The 5th edition of Targeting Mitochondria 2014 was a huge success
The 5th World Congress on Targeting Mitochondria was held on October 29 to 31, 2014, at Hotel Ritz Carlton, Berlin. It was a huge success gathering more than 460 attendees from 36 countries were welcomed. The participants were coming from various fields: academics, industrials, clinicians...
To access to the pictures gallery organized in three parts (workshop and second / third day of conference), please click here.
Pr Martin Kerschensteiner was awarded by the Scientific Committee of World Mitochondria Society for his Scientific Contribution
It is an honor to announce the award discerned by The Scientific Committee of WMS to Pr. Martin Kerschensteiner from Medical Center of the University of Munich, Germany for his scientific contribution about "Microscopy enables dynamic and functional analysis of mitochondria in vivo", during Targeting Mitochondria 2014.
According Pr. Martin Kerschensteiner: "Here, I want to discuss how recent advances in light microscopy can improve our understanding of mitochondrial pathology in diseases of the nervous system. Over the recent years we have developed optical approaches that allow us to visualize the structure, dynamic behavior and molecular make-up of mitochondria changes in the living nervous system. I will use our work on traumatic and inflammatory axon damage in the spinal cord as examples to illustrate how these imaging approaches can help us to better understand when and where mitochondrial pathology evolves in neurons, which mechanisms induce it and how it may be prevented."
For more information about Targeting Mitochondria 2014: www.targeting-mitochondria.com
WMS discerned the award of Short Oral Presentation to Dr. Nina Entelis
Dr. Nina Entelis, from University of Stasbourg, France was awarded for her Short Oral Presentation by WMS Scientific Committee during the 5th International Congress on Targeting Mitochondria which was held in Berlin on October 29-30-31.
During Targeting Mitochondria 2014, Dr. Nina Entelis gave a presentation about "Design of therapeutic anti-replicative RNA imported into mitochondria of human cells.".
According Dr. Nina Entelis: "Mutations in mitochondrial genome (mtDNA) have been associated with a wide variety of human disorders. In patients with mtDNA defects, it is common to find mutant and wild type mtDNA molecules in the same cell, the phenomenon known as heteroplasmy. Manifestation of biochemical and clinical defects occurs only when a threshold level of heteroplasmy (generally, >60% of mutant genomes) has been reached. Since there is no efficient treatment for these disorders, one attractive approach would be to specifically target mutant mtDNA and prevent it from replicating, thereby giving an advantage to the propagation of wild type genomes.
This strategy is confronted to two problems: translocation of anti-genomic oligomers through the double mitochondrial membrane, and their access and specific binding to mutated region of mtDNA. Our study of the natural pathway of RNA import into mitochondria permitted to identify the import determinants in tRNA and 5S rRNA structures. Basing on these data, a set of small RNA molecules with significantly improved efficiency of mitochondrial targeting was designed[1,2].
To target therapeutic oligonucleotides into deficient human mitochondria, we inserted short sequences corresponding to the boundaries of a large deletion in mtDNA[3] or to the region of a point mutation[4] into importable RNAs. We demonstrated that recombinant RNA molecules containing determinants for mitochondrial import and 20-nucleotide sequence corresponding to the mutated region of mtDNA, are able to anneal selectively to the mutated mitochondrial genomes. After import into mitochondria of cultured human cells, these RNAs induced a decrease of the proportion of mtDNA bearing a pathogenic mutation.
To improve the stability of anti-replicative RNA molecules in human cells, we introduced into these molecules various chemically modified oligonucleotides and tested their impact on the efficiency of their hybridisation with mtDNA in vitro, RNA stability, mitochondrial targeting and the effect on heteroplasmy in human cybrid cells in culture[5]. We also demonstrated that anti-replicative RNA molecules conjugated with cholesterol are able to penetrate into cultured cells without additional lypophilic agents.
Another way to obtain a shift of heteroplasmy level consists in stable expression of anti-replicative molecules in cells. We therefore developed cybrid cell lines expressing recombinant 5S rRNA molecules and demonstrated an important and stable decrease of their heteroplasmy level.
These studies clearly show that RNA import into mitochondria is a perspective tool suitable for biomedical applications.
This work was supported by the CNRS, Strasbourg University and grants Labex MitoCross, LIA ARN-Mitocure, AFM, ANR, FRM and Suprachem."
For more information about Targeting Mitochondria 2014: www.targeting-mitochondria.com
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