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
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
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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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 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
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
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
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
