Mitochondria in Retinal Photoreceptors: More than Meets the Eye
Dr. John Ball, from National Institutes of Health, USA, will join us this year to present his most recent findings on the "Mitochondria in Retinal Photoreceptors: More than Meets the Eye".
In the mammalian retina, each cone photoreceptor contains a multitude of mitochondria that appose its outer segment, where photons are detected and translated into bioelectrical signals that lead to perception of light.
Dr. Ball shows that—in addition to their customary energetic role—this mitochondrial agglomeration functions as a microlens that enhances the availability of light at the outer segment. This optical role has implications for both vision and for the diagnosis of retinal disease.
Join us in Targeting Mitochondria 2022 to learn about the many major roles of mitochondria and benefit from the experience of professional researchers like Dr. Ball. Book your spot.
Targeting Mitochondria 2022 Congress
October 26-28, 2022 - Berlin, Germany
wms-site.com
Mitochondrial targeting in aging and injury
Dr. Raghavan Pillai Raju, from the Medical College of Georgia, USA will join us this year to present his most recent findings on "Mitochondrial targeting in aging and injury".
Dr. Raju's laboratory is interested in understanding the alterations in mitochondrial function with aging and injury and developing strategies that target mitochondria to restore metabolic coordinates following acute injury. He will also discuss the resilience of young animals to injury and the rejuvenating effect of plasma-derived extracellular vesicles from young animals in potentiating mitochondrial function and improving survival following hemorrhagic shock injury in aged animals.
Targeting Mitochondria 2022 Congress
October 26-28, 2022 - Berlin, Germany
www.targeting-mitochondria.com
Mitochondrial Transfer via MitoPunch
Dr. Michael Teitell, from the University of California, USA will join us this year to present his most recent findings on "Mitochondrial Transfer via MitoPunch".
He will be discussing the use of MitoPunch to deliver mitochondria containing mitochondrial DNA (mtDNA) into cells lacking mtDNA.
Targeting Mitochondria 2022 Congress
October 26-28, 2022 - Berlin, Germany
www.targeting-mitochondria.com
2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness
Dr. Ian J. Holt, from the Biodonostia Health Research Institute, Spain will join us this year to present his most recent findings on "2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness".
Ever since mutant mitochondrial DNA was discovered to cause human diseases researchers have sought to understand how defective mitochondria evade natural selection, and to find ways to combat them. Most mutant mitochondrial DNA variants cause disease only when they account for substantially more than half the total population of molecules, and so decreasing the level of the mutants by a small amount can produce dramatic improvements in mitochondrial function.
Dr. Holt discovered that the replication of mutant mitochondrial DNA is equal to that of wild-type molecules when nutrients are plentiful; however, nutrient restriction inhibits the replication of mutant mtDNA. Using small molecules that limit nutrient consumption he then decreased the mutant load in cells of patients with mitochondrial DNA disease.
These findings indicate the parasitic nature of mitochondria with mutant mtDNA and identify a highly promising therapeutic strategy that we are advancing towards the clinic.
Targeting Mitochondria 2022 Congress
October 26-28, 2022 - Berlin, Germany
www.targeting-mitochondria.com
Mitochondrial responses to a massive trauma-determinant of survival
Dr. Marc G. Jeschke, from the University of Toronto, Canada will join us this year to present his most recent findings on "Mitochondrial responses to a massive trauma-determinant of survival".
He will be introducing us to the mitochondrial function and associate metabolic changes in a model of severe trauma. He will also delineate changes associated with age.
Targeting Mitochondria 2022 Congress
October 26-28, 2022 - Berlin, Germany
www.targeting-mitochondria.com
Unlocking the potential of the mammalian electron transport chain
Dr. Jessica Spinelli, from the Whitehead Institute for Biomedical Research, USA will join us this year to present her most recent findings on "Unlocking the potential of the mammalian electron transport chain".
The continuous flow of electrons in the mitochondrial electron transport chain (ETC) is required for an array of mammalian biosynthetic and bioenergetic pathways. Removal of electrons onto a terminal electron acceptor (TEA), which is known to be oxygen in mammalian cells, maintains continuous electron flow in the ETC. Paradoxically, in low oxygen environments, mammalian cells still catalyze reactions that necessitate electron flow in the ETC, suggesting the existence of alternative mechanisms to remove ETC electrons beyond oxygen reduction.
Here, Dr. Spinelli uncovers a secondary TEA that sustains electron flow in the mammalian ETC upon hypoxia exposure. In mice, the ability to use this adaptive electron removal pathway is tissue-specific and dependent on the presence of a previously uncharacterized mammalian metabolite.
Targeting Mitochondria 2022 Congress
October 26-28, 2022 - Berlin, Germany
wms-site.com
EV-Mitochondria as a Promising Therapeutic for Mitochondrial Dysfunction
Dr. Devika S Manickam, from Duquesne University, USA will join us this year to present her most recent findings on "EV-Mitochondria as a Promising Therapeutic for Mitochondrial Dysfunction" in a special session dedicated to "Extracellular Vesicles & Mitochondria: The Target" .
Extracellular vesicles (EVs) are natural, cell-secreted nanoparticles that play an important role in intercellular communication. Dr. Manickam's work has demonstrated that the innate mitochondrial load in EVs can be used to increase the cellular energetics and mitochondrial function of the recipient brain endothelial cells. She has also demonstrated that the EV mitochondrial cargo can be transferred mouse brain slice neurons. She is currently engineering EVs with a greater mitochondrial load via pharmacological activation of the donor cells.
Dr. Manickam's talk will describe how the EV mitochondrial load can serve as a therapeutic modality to treat neurodegenerative diseases.
Remember, you can share abstracts related to this special session and get the chance to participate in Targeting Mitochondria 2022.
Targeting Mitochondria 2022 Congress
October 26-28, 2022 - Berlin, Germany
wms-site.com
A Novel PTD-mediated IVT-mRNA delivery platform developed for Protein Replacement Therapy (PRT) for genetic/metabolic disorders: the case of human fatal infantile cardioencephalomyopathy attributed to SCO2 mutations
Lefkothea C. Papadopoulou, Professor of Pharmacology, from Aristotle University of Thessaloniki, Greece, will join us this year to present her most recent findings on "A Novel PTD-mediated IVT-mRNA delivery platform developed for Protein Replacement Therapy (PRT) for genetic/metabolic disorders: the case of human fatal infantile cardioencephalomyopathy attributed to SCO2 mutations".
Mutations in human SCO2 gene, encoding the mitochondrial inner membrane Sco2 COX assembly protein, have been implicated in the mitochondrial disorder fatal infantile cardioencephalomyopathy accompanied by cytochrome c oxidase (COX) deficiency as well in neurodegenerative disorders, like Leigh syndrome.
Since there is no effective treatment for such disorders yet, a Protein Replacement Therapeutic (PRT) approach via the Protein Transduction domain (PTD) Technology was explored. Protein Transduction Domains (PTDs) or Cell Penetrating Peptides (CPPs), such as TAT, are small peptides, able to facilitate intracellular delivery of a variety of cargos, ranging from small molecules to macromolecules, and permit their localization in subcellular organelles, like mitochondria. In the frame of this work, Dr. Papadopoulou's group cloned the coding sequences of human SCO2 gene and expressed it in bacteria to produce the recombinant human TAT-L-Sco2 fusion protein.
Purified bacterial inclusion bodies, enriched in the fusion protein, were solubilized in 1M L-Arg solution. Exogenously administered TAT-L-Sco2 fusion protein was transduced successfully inside the mitochondria, where it was processed by MPP to yield the mature Sco2 protein, thus contributing to COX assembly and recovery of COX activity in fibroblasts derived from a SCO2/COX deficient patient. Radiolabeled TAT-L-Sco2 fusion protein, prepared and administered in animals (mice), was found to be biodistributed in peripheral tissues and successfully transduced into mitochondria in vivo.
Since the production of recombinant protein therapeutics requires complex purification procedures, increasing the cost of good manufacturing practice (GMP)’s protein products, Dr. Papadopoulou's group moved on to an alternative PRT approach, the PTD-mediated transduction of the vitro transcribed (IVT)-mRNAs. IVT-mRNA, produced in a cell-free system, resembles natural mRNA and its successful intracellular delivery permits transient expression / translation into the protein of interest.
The IVT-mRNA Technology platform has been optimized, in terms of IVT-mRNA structural stability, sensitivity to enzymatic degradation, inadequate translation and immunogenicity. Several structural and chemical modifications in IVT-mRNA increased the amount of protein produced per molecule of delivered mRNA, while reduced its immunogenicity. Furthermore, the potential clinical applications of the IVT-mRNAs strongly depend on their successful delivery to produce enough of the desired protein intracellularly. A wide range of in vitro and in vivo transfection reagents have been shown to facilitate IVT-mRNAs intracellular uptake, including protection from degradation.
Having all these in mind, Dr. Papadopoulou's group developed a novel PTD-mediated IVT-mRNA delivery platform [International Patent Pending, PCT/GR2020/000059; Greek patent: 1010063 (National)] as a protein therapy approach for metabolic / genetic disorders, using the amphipathic PTD, PFVYLI. The selected PTD is exploited as a carrier for any therapeutic IVT-mRNA through a novel, covalent reaction, with puromycin (conjugated via an amide bond to the PTD) served as a linker to the IVT-mRNA. PTD was successfully conjugated to IVT-mRNA of SCO2, as confirmed by NMR data analysis and a band shift assay compared to the corresponding naked IVT-mRNA.
The proposed PTD-IVT-mRNA delivery platform showed significant stability of the studied IVT-mRNA in various conditions, indicating that the PTD protects the IVT-mRNA from immediate nuclease digestion. PTD-IVT-mRNA of SCO2 was successfully transduced (via clathrin-mediated endocytosis) into fibroblasts derived from a SCO2/COX deficient patient and led to the recovery of reduced COX activity, compared to the naked IVT-mRNA as well the IVT-mRNA conjugated to a non-PTD, Control peptide.
These findings suggest that this novel PTD-IVT-mRNA delivery strategy could be a promising platform for effective gene expression/translation into a protein of interest, with the potential to be used in clinical trials as a PRT for metabolic/genetic disorders.
Targeting Mitochondria 2022 Congress
October 26-28, 2022 - Berlin, Germany
wms-site.com
