Nuclear Sensing of Breaks in Mitochondrial DNA Enhances Immune Surveillance

Targeting Mitochondria 2021 sfeir-agnelDr. Agnel Sfeir from Memorial Sloan Kettering Cancer Center, USAwill give a presentation on :Nuclear Sensing of Breaks in Mitochondrial DNA Enhances Immune Surveillance"

Dr. Sfeir will describe mitochondrial DNA double-strand breaks (mtDSBs) as toxic lesions that compromise the integrity of mitochondrial DNA (mtDNA) and alter mitochondrial function. Communication between mitochondria and the nucleus is essential to maintain cellular homeostasis; however, the nuclear response to mtDSBs remains unknown. Here, using mitochondrial-targeted transcription activator-like effector nucleases (TALENs), we show that mtDSBs activate a type-I interferon response that involves the phosphorylation of STAT1 and activation of interferon-stimulated genes. After the formation of breaks in the mtDNA, herniation mediated by BAX and BAK releases mitochondrial RNA into the cytoplasm and triggers a RIG-I-MAVS-dependent immune response. We further investigated the effect of mtDSBs on interferon signalling after treatment with ionizing radiation and found a reduction in the activation of interferon-stimulated genes when cells that lack mtDNA are exposed to gamma irradiation. We also show that mtDNA breaks synergize with nuclear DNA damage to mount a robust cellular immune response. Taken together, we conclude that cytoplasmic accumulation of mitochondrial RNA is an intrinsic immune surveillance mechanism for cells to cope with mtDSBs, including breaks produced by genotoxic agents.

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

 

Impact of Mitochondrial Dynamics on Stem Cell Function: Insights from Physiology, Diseases and Aging

mireille

Dr. Mireille Khacho, from Faculty of Medicine, University of Ottawa, Canada will be joining the Targeting Mitochondria 2021 World Congress, which will be held October 27-29, 2021 and will present her study on "The Impact of Mitochondrial Dynamics on Stem Cell Function: Insights from Physiology, Diseases and Aging".

 

 

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

 

Age-Related Mitochondrial Dysfunction as a Key Factor in COVID-19 Disease

miDr. Guillermo López-Lluch from Universidad Pablo de Olavide-CSIC, Spain will be joining the Targeting Mitochondria 2021 World Congress, which will be held October 27-29, 2021 and give a presentation on Age-related Mitochondrial Dysfunction as a Key Factor in COVID-19 Disease.

Dr. Lluch states that COVID-19 and other respiratory diseases induce an inflammatory response mainly produced by the release of inflammatory cytokines. In this response, lymphocyte release of interferon decrease impairing the immune response against virus infection. In both, inflammatory response and inhibition of interferon release, activity of mitochondria plays a key role. Accumulation of dysfunctional mitochondria during aging and chronic metabolic diseases can be the key of the inefficient response against respiratory infections.

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

 

 

Clinical Application of Antioxidants to Improve Human Oocyte Mitochondrial Function: Advances and Perspective

MitoDr. Cristina Rodríguez-Varela from Medical Research Institute Hospital La Fe (IIS La Fe) in Valencia, Spain will give a presentation on Clinical Application of Antioxidants to Improve Human Oocyte Mitochondrial Function: Advances and Perspective.

Dr. Rodríguez-Varela will discuss the fact that mitochondria are essential organelles in the acquisition of human oocyte competence, as sufficient energy levels are crucial for optimal oocyte maturation, fertilization and subsequent embryo development. In addition, mitochondria constitute the first antioxidant line of defense within the cell, counteracting reactive oxygen species (ROS) derived from its own metabolism. An imbalance between the amount of ROS produced and the capacity of the cell to counteract them leads to oxidative stress, and ultimately to mitochondrial dysfunction. This dysfunction, in turn, impairs cellular functions through reduced ATP output and/or increased oxidative stress. Hence, oxidative stress may be the cause of, or be caused by, mitochondrial dysfunction. Regardless of the origin, this condition gives rise to a vicious cycle with positive feedback, ultimately compromising the overall oocyte quality. Antioxidant therapy has arisen in this context as a new approach aiming to improve human oocyte quality by means of improving, or just protecting, mitochondrial function. In this talk, we will highlight the importance of optimal levels of functional mitochondria in the acquisition of human oocyte competence, and we will give an overview of the main antioxidant supplementation therapies currently under research in our species.

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

Extracellular Mitochondria for Therapy and Diagnosis in Stroke

Targeting Mitochondria 2021 Kazuhide Hayakawa-v2

Dr. Kazuhide Hayakawa, Assistant Professor at Harvard Medical School/ Massachusetts General Hospital, USA will join the Targeting Mitochondria 2021 congress which will be held on October 27-29, 2021 and give a presentation entitle "Extracellular Mitochondria for Therapy and Diagnosis in Stroke".

Recent accumulating findings in cell were provided by Dr. Hayakawa, as well as in animals and humans. These studies suggest that mitochondria maybe surprisingly present in extracellular space andregulatea non-cell-autonomous mechanism in the CNS by mediating injury and recovery. Given that extracellular mitochondria are passively secreted by damaged cells or released from activated cells, it may allow us to look into the metabolic status to diagnose overall disease severity or progress of repair. Moreover, exogenous mitochondrial transplantation may protect neurons in acute CNS injury. Further studies are warranted to carefully assess whether extracellular mitochondria serve as a novel class of biomarkers and whether the putative transfer of mitochondria between cells in the CNS can be leveraged to augment recovery after stroke or neurodegenerative diseases.

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

Big Change from Small Player - Mitochondria Alter Body Metabolism and Gene Expression

Targeting Mitochondria 2021 Scott Balinger-V5Prof. Scott Ballinger from University of Alabama at Birmingham, USA will be joining the Targeting Mitochondria 2021 World Congress, which will be held October 27-29, 2021 and give a presentation on "Big Change from Small Player - Mitochondria Alter Body Metabolism and Gene Expression".

 

 

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

Mitochondrial Transplantation Therapy, the Recent Advances and Perspective

Targeting Mitochondria 2021 James McCullyDr. James McCully, from the Harvard Medical School Department of Cardiac Surgery Boston Children’s Hospital, USA, will be joining the Targeting Mitochondria 2021 World Congress, which will be held October 27-29, 2021.

Dr. McCully will present his recent study on "Mitochondrial Transplantation Therapy, the Recent Advances and Perspective" during the congress.

Dr. McCully’s research focuses on the mechanisms and subcellular localization of the biochemical and molecular events contributing to myocardial cell death. In particular, his lab has investigated the discriminant and/or coordinate mechanisms leading to ischemia/reperfusion injury in the neonate, child, mature and aged male and female with particular emphasis on the development of novel and specific cardioprotective protocols. 

Recently he has developed a novel approach to cardioprotection using autologous mitochondrial transplantation. His research has demonstrated that transplantation of autogeneic mitochondria into the ischemic zone of the myocardium during early reperfusion significantly enhances post-ischemic functional recovery.

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

 

Regulation of Physiological Mitophagy

Targeting Mitochondria 2021 Dr. Thomas McWilliamsProf. Thomas G. McWilliams from University of Helsinki, Finland will join the Targeting Mitochondria 2021 congress and will present his research on "Regulation of Physiological Mitophagy".

Prof. McWilliams demonstrates that mitochondrial network dysfunction is neutralised by the selective autophagy of mitochondria (mitophagy). Mitophagy is widely thought to be a disease-relevant process and is routinely implicated in neurodegenerative pathology and mammalian aging. Yet, most of our knowledge and assumptions about mitophagy are derived from its induction as a PINK1-Parkin-dependent stress-responsein vitro. Converging data from multiple mitophagy reporter models suggests that this process is much more complex in tissues than previously appreciated. Mitophagy is a highly pervasive and heterogeneous processin vivo, that proceeds normally in the absence of the PINK1-Parkin signalling pathway. Using a multi-OMICs approach, we have defined the progression and regulation of PINK1-independent mitophagy, deciphering its integration with other homeostatic pathways to safeguard cellular and metabolic integrity.
 

Key Publications

McWilliams TG*,Prescott AR, Montava-Garriga L, Brooks SP, Singh F, Barini E, Muqit MM and Ganley IG*(2018a)
Basal mitophagy occurs independently of PINK1 in mouse tissues of high-metabolic demand. Cell Metabolism Feb 06; 27(2): 439-449. 

McWilliams TG* et al., (+28 Authors) Ganley IG, Suomalainen A, Muqit MMK*(2018b).
Phosphorylation of Parkin at Serine65 is essential for its activation in vivo.
Open Biology. Nov8:180108. 

Suomi F & McWilliams TG*(2019)
Autophagy in the nervous system: a primer for neuroscientists.
Neuronal Signaling 3 (3): NS20180134.

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

 

Mechanism of Membrane-Tethered Mitochondrial Protein Synthesis

Targeting Mitochondria 2021 Antoni BarrientosDr. Antoni Barrientos from University of Miami Miller School of Medicine, USA will give a presentation entitled "Mechanism of Membrane-Tethered Mitochondrial Protein Synthesis".

The main research interest of their laboratory is on the basic mechanisms that govern the biogenesis of mitochondrial protein complexes in health, disease and aging. They are most specifically interested in the assembly and function of the mitochondrial translation machinery and of the mitochondrial respiratory chain and oxidative phosphorylation system components, involved in biological energy transduction.

The study of mitochondria is now a very “hot issue” for both basic and clinical research. Mitochondria are not only the “energy factories” of the cell but they also house a multiplicity of pathways that serve to regulate cellular life and death. Importantly, mitochondria are involved in prevalent human diseases of wide social impact, most notably neurodegenerative disorders, but also in cancer and the aging process.

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Online
www.targeting-mitochondria.com

Cardiorespiratory Fitness and Mitochondrial Health as Modulators of COVID-19

Targeting Mitochondria 2021 BurtscherDr. Johannes Burtscher, from University of Lausanne, Suisse will join the Targeting Mitochondria 2021 Congress and will give a presentation entitled "Cardiorespiratory Fitness and Mitochondrial Health as Modulators of COVID-19".

Dr. Burtscher confirms that some coronaviruses like SARS-CoV-2, the pathogen causing COVID-19, manipulate host cell mitochondria to dodge the host immune defense. We hypothesize that good mitochondrial health, for example due to regular exercise and associated with cardiorespiratory fitness, protects from viral manipulation of mitochondria. Conversely, mitochondrial damage may facilitate viral infection and aggravate the disease. I will summarize the theoretical interactions of SARS-CoV-2 with host mitochondria and provide an overview of recent studies investigating the link between COVID-19 and cardiorespiratory fitness and mitochondrial health.

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

Mitochondrial Arginase-2 is Essential for IL-10 Metabolic Reprogramming of Inflammatory Macrophages

targeting mitochondria 2021 Dr. Claire McCoyDr. Claire McCoy from Royal College of Surgeons in Ireland, Ireland will join the Targeting Mitochondria 2021 Congress and give a presentation about "Mitochondrial Arginase-2 is Essential for IL-10 Metabolic Reprogramming of Inflammatory Macrophages".

Dr. Claire McCoy graduated in Biochemistry from Trinity College Dublin and completed her PhD at the University of Dundee, Scotland in 2006. Her first postdoctoral position in Innate Immunology was completed at Trinity College Dublin, during which time she was awarded a prestigious Marie Curie International Fellowship. She joined the Hudson Institute, Melbourne as a Research Fellow in 2010 and obtained a New Investigator Project Grant from the NHMRC to continue her work investigating the role of microRNAs in Inflammatory diseases. Claire joined RCSI as the Immunology lecturer in August 2016, where she now leads the growing microRNA Inflammation research group. Claire was the recipient of an SFI Future Research Leader's award presented by President Higgins in January 2018.

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

A session dedicated to Nuclear-mitochondrial interactions and their effect on longevity and health will be organized

A session dedicated to the "Nuclear-mitochondrial interactions and their effect on longevity and health" will be organized by Prof. Miria Ricchetti, Team Stability of Nuclear and Mitochondrial DNA, Institut Pasteur, France that will chair the session.

Among the speakers:

Targeting Mitochondria 2021 Miria-Ricchetti-С1Introduction & Presentation of Session
Dr. Miria Ricchetti, Team Stability of Nuclear and Mitochondrial DNA, Institut Pasteur, France

Targeting Mitochondria 2021 Jose Antonio EnriquezDeciphering strategic interactions between mitochondrial and nuclear genome
Dr. José Antonio Enríquez from Centro Nacional de Investigaciones Cardiovasculares Carlos III, Spain

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

 

Deciphering strategic interactions between mitochondrial and nuclear genome

Targeting Mitochondria 2021 Jose Antonio EnriquezDr. José Antonio Enríquez from Centro Nacional de Investigaciones Cardiovasculares Carlos III, Spain. Dr. Enríquez  will give a presentation entitled "Deciphering strategic interactions between mitochondrial and nuclear genome".

Dr. Enríquez has done probably the most advanced studies on nuclear-mitochondrial interactions and their effect on organisme longevity and health. He focuses on distinct combinations of nuclear and mitochondrial genomes and their effect at the organismal level (lifespan, health condition, predisposition to disease), as well as investigates the underlying mechanism including respiratory complexes and supercomplexes.
Last year he published a seminal paper  in Science Advances showing the dynamics of non-pathogenic heteroplasmy (segregation of one of the two mtDNA genomes in different tissues) and their dependence on OXPHOS performance (PMID: 32832682). See also a recent review (PMID: 33369015) on the interactions between mitochondrial and nuclear genome.

mitochondria figure

Heteroplasmic mouse models harboring in the same cytoplasm, different non‐pathological mtDNA variants‐haplotypes. MtDNA preference is cell‐type‐specific and not tissue‐specific. Also, the metabolic differentiation program determines the preferred mtDNA haplotype and the mtDNA segregation is driven by functional selection and strongly modulated by the crosstalk between the nucleus and mitochondria.  © 2020 The Authors. IUBMB Life
https://doi.org/10.1002/iub.2434

 

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin & Virtual Congress
www.targeting-mitochondria.com

 

Circulating Mitochondrial DNA as an Early Indicator of Severe Lung Disease

Targeting Mitochondria 2021 Andrew E GelmanProf. Andrew E. Gelman from Washington University School of Medicine, USA will give a presentation entitled "Circulating Mitochondrial DNA as an Early Indicator of Severe Lung Disease".

Prof. Gelman will discuss how cell-free mitochondria DNA levels have been used to evaluate the severity of solid organ injury.  He will also cover the implications of cell-free mitochondrial DNA findings in several pulmonary diseases including COVID-19. Additionally, Prof. Gelman will talk about the possible tissue origins of cell-free mitochondria DNA and whether it is the result of an overexuberant immune response or a sign of mitochondrial dysfunction.

Targeting Mitochondria 2021 Congress
October 27-29, 2021 - Berlin, Germany & Virtual Congress
www.targeting-mitochondria.com

 

The Bioenergetics Consequences of Winter Cold in Small Birds

Targeting Mitochondria 2021 Andreas NordDr. Andreas Nord, researcher in evolutionary ecology at Lund University, Sweden, will present his study on "The Bioenergetics Consequences of Winter Cold in Small Birds".

Dr. Nord highlighted: "Small birds at high latitude face converging energetic challenges in winter, when low air temperature increases the energy cost of staying warm at the same time as short day length and snow constrain refuelling opportunities. The thermoregulatory adaptations that permit existence in such environments are well studied on organismal levels, but analogous processes in the cellular machinery fuelling thermoregulation are poorly understood. In this talk, I will outline how seasonal and diurnal changes in mitochondrial function interact with whole-animal physiology to help birds stay warm when it is cold".

Please follow this link to read detailed news on his research.

 

Targeting Mitochondria 2021 Congress
October 27-29, 2021
Berlin, Germany & Virtual Congress
www.targeting-mitochondria.com