Environmental factors heavily impact on human health and behaviors. Mitochondria are key modulators of cellular homeostasis and may represent central hubs in response to different types of environmental and nutritional interventions. Through state-of-the-art approaches our lab exploits the nematode Caenorhabditis elegans to unravel molecular mechanisms of mitochondrial adaptation to extrinsic interventions (e.g. food components, hypoxia, pollution related particles) in modulating age- and disease-associated neurodegenerative processes, with the ultimate goal of extending healthy lifespan. To this end, we recently also developed a high-content phenotype-based screening strategy to identify compounds acting through mitochondria to protect against age- and disease-associated neurodegeneration.
1. Mechanistic aspects of mitochondrial-stress control of longevity
Through complementary genetic, biochemical and molecular approaches we investigate intracellular players affected by mitochondrial-targeting genetic and pharmacological interventions to promoting healthy aging. Targeted (autophagy, apoptosis, neuronal specific pathways) as well as unbiased strategies are concurrently used in this project funded by the Competitive Research Funding of the Medical Faculty of the Heinrich Heine University and by the DFG. Long-standing collaborations with Profs Nektarios Tavernaraki, Bart Braeckman and Hilde Nilsen are nicely contributing to this project.
2. Environmental interventions acting through mitochondria to modulate health and lifespan
In this DFG funded project we optimized a high-content phenotypic-based screening microscopy platform that will be exploited to identify environmental factors (toxins, food component, radiations) acting through mitochondria during animal development to induce neuronal toxicity or promote healthy aging. We validated our platform using genetic and pharmacological interventions known to extend C. elegans lifespan and identified a new mitochondrial ATPase inhibitor with lifespan extending effects. Recently established collaboration with the Haendeler lab and Dr Ralph Menzel are constructively contributing this project.
3. C. elegans models for human mitochondrial-associated diseases (HMAD)
We developed C. elegans models for different HMAD that nicely reproduce disease progression and we are characterizing mitochondrial and neuronal deficits in these models through a combination of behavioral and biochemical assays. The ultimate goal of this project funded by the Strategic Research Funding of the Heinrich Heine University and the DFG is to identify key molecular players of disease pathogenesis for targeted therapeutic interventions (pharmacological, nutritional or natural compounds) to eventually test in corresponding mammalian diseases models. To achieve this last aim we have an established ongoing collaboration with Dr. med. Felix Distelmeir at the pediatric clinic of the HHU Hospital.
Haarmann-Stemmann research group
Krutmann research group
Schikowski research group
Schins research group
Dr. Felix Distelmeir, Centre for Child and Adolescent Medicine, University Hospital
Dr. Mathias Beller, Institute for Mathematical Modelling of Biological Systems
Prof. James Adjaye, Institute for Stem Cell Research and Regenerative Medicine (ISRM)
Prof. Björn Schumacher, CECAD Research Center, University of Cologne
PD Dr. Ralph Menzel, Humboldt-Universität zu Berlin
Dr Nuno Raimundo, Institute of Cellular Biochemistry, Universitätsmedizin Göttingen
Prof. Nektarios Tavernarakis, Institute of Molecular Biology and Biotechnology Foundation for Research and Technology-Hellas Medical School, University of Crete, Heraklion, Greece
Prof. Bart Braeckman, Biology Department, Ghent University, Belgium
Prof. Hilde Nilsen, Institute of Clinical Medicine, University of Oslo, Norway and Department of Clinical Molecular Biology, Akershus University Hospital, Lørenskog, Norway
Prof. Francesco Cecconi, European Center for Brain Research
Santa Lucia Foundation, Rome, Italy &
Danish Cancer Society research Center, Cancer Center, Kopenhagen, Denmark
Prof. Frank Madeo, Institute for Molecular Biosciences, Graz University, Austria
Maglioni S, Mello DF, Schiavi A, Meyer J, Ventura N. “Mitochondrial bioenergetics changes during development as an indicator of C. elegans health-span. Aging (Albany NY). 2019 Aug 27;11(16):6535-6554.
Torgovnick A*, Schiavi A*, Shaik A^, Kassahun H^, Maglioni S, Rea SL, Johnson TE, Reinhardt HC, Honnen S, Schumacher B, Nilsen H, Ventura N. “BRCA1/BARD1 mediate apoptosis resistance but not longevity in response to mitochondrial stress in C. elegans.” EMBO Reports. 2018 Oct 26. Dec;19(12). pii: e458568.
Eckers A, Jakob S, Heiss C, Haarmann-Stemmann T, Goy C, Brinkmann V, Cortese-Krott MM, Sansone R, Esser C, Ale-Agha N, Altschmied J, Ventura N*@, Haendeler J.*@ “The aryl hydrocarbon receptor promotes aging phenotypes across species. Sci Rep. 2016 Jan 21;6:19618.
Maglioni S, Arsalan N, Franchi L, Hurd A, Opipari AW, Glick GD, Ventura N. “An automated phenotype-based microscopy screen to identify pro-longevity interventions acting through mitochondria in C. elegans”, Biochim Biophys Acta Bioenergetics. 2015 Nov; 1847(11):1469-78.
Schiavi A, Maglioni S, Palikaras K, Shaik A, Strapazzon F, Brinkmann V, Castelein N, Henau S, Torgovnick A, Braeckman BP, Cecconi F, Tavernarakis N, Ventura N. “Iron starvation-induced mitophagy mediates lifespan extension upon mitochondrial stress in C. elegans”, Curr Biol. 2015. 25(14):1810-22.