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Group leader: Mitochondria in neuromuscular pathologies: Mechanisms, Prevention and Therapy

PD Natascia Ventura MD, PhD
Institute of Clinical Chemistry and Laboratory Diagnostic
Medical Faculty, Heinrich Heine University;
&
and the IUF- Leibniz Research Institute for Environmental Medicine
Auf’m Hennekamp 50
40225 Düsseldorf


Research Interest

Mitochondria are key players in cellular energy homeostasis and integrate responses to genetic and environmental/nutritional factors which concurrently shape health and aging. The overall aim of Ventura lab is to address the role of mitochondria in developmental- as well as age-associated neurodegenerative diseases, with the ultimate goal of promoting health-span. To this end, we are interested in identifying mitochondrial cell-autonomous and non-autonomous responses to environmental/dietary factors (i.e. food components and contaminants, drugs) of relevance for neuronal pathologies prevention and treatment. Based on past and current findings special attention is revolved towards mitochondria-regulated cell death and survival pathways as well as lipid and iron homeostasis.

The lab primarily exploits the nematode Caenorhabditis elegans, a powerful genetic tractable multicellular organism to study neuronal pathologies and aging, for complementary in vivo behavioral, genetic and live-imaging approaches and has recently established  a high-content phenotype-based screening platform. The use of different cell lines was lately implemented in the lab, also thanks to local and international collaboration partners, to translate results into relevant mammalian disease models (e.g. Alzheimer disease, Mitochondria complex I deficiency).

Ongoing lab projects
  • Nutritional targeting of the mitochondria-tyr-kinase axis to prevent age-associated neuronal decline – MiTyrAge (BMBF)
  • Identification of compounds ameliorating neurodevelopmental deficits in newly established C. elegans and cellular models for Mitochondrial complex I deficiency (DFG)
  • Role of mitochondria in neuronal aging induced by environmental nanoparticles (DFG)
  • AhR-mitochondria crosstalk in diet promoted longevity (DFG)
Further information
Selected Publications (past 5 years)
  1. Brinkmann V, Schiavi A, Shaik A, Puchta D, Menzel R, Ventura N. (2020) Diet and environmental factors have opposite AhR-dependent effects on C. elegans healthspan. Aging (Albany NY). 2020 Dec 13;13(1):104-133. DOI: 10.18632/aging.202316
  2. Schiavi A, Strappazzon F, Ventura N. (2020). Iron metabolism regulated mitophagy in aging and associated neuronal pathologies. Mech Age Dev. Jun;188:111252. DOI: 10.1016/j.mad.2020.111252
  3. Maglioni S, Mello DF, Schiavi A, Meyer J, Ventura N. (2019) Mitochondrial bioenergetics changes during development as an indicator of C. elegans health-span. Aging (Albany NY). Aug 27;11(16):6535-6554. DOI: 10.18632/aging.102208
  4. Carmona-Gutierrez D, Zimmermann A, Kainz K, Pietrocola F, Chen G, Maglioni S, Schiavi A, Nah J, Mertel S, Beuschel CB, Castoldi F, Sica V, Trausinger G, Raml R, Sommer C, Schroeder S, Hofer SJ, Bauer MA, Pendl T, Tadic J, Dammbrueck C, Hu Z, Ruckenstuhl C, Eisenberg T, Durand S, Bossut N, Aprahamian F, Abdellatif M, Sedej S, Enot DP, Wolinski H, Dengjel J, Kepp O, Magnes C, Sinner F, Pieber TR, Sadoshima J, Ventura N, Sigrist SJ, Kroemer G, Madeo F. (2018) The flavonoid 4,4’-dimethoxychalcone promotes autophagy-dependent 3 longevity across species. Nat Commun. Feb 19;10(1):651. DOI: 10.1038/s41467-019-08555-w
  5. Torgovnick A*, Schiavi A*, Shaik A^, Kassahun H^, Maglioni S, Rea SL, Johnson TE, Reinhardt HC, Honnen S, Schumacher B, Nilsen H, Ventura N. (2018) BRCA1/BARD1 mediate apoptosis resistance but not longevity in response to mitochondrial stress in C. elegans. EMBO Reports. Dec;19(12). pii: e45856. DOI: 10.15252/embr.201845856
  6. Majora M, Sondenheimer K, Knechten M, Uthe I, Esser C, Schiavi A, Ventura N, Krutmann J. (2018) HDAC inhibition improves autophagic and lysosomal function to prevent loss of subcutaneous fat in a mouse model of Cockayne syndrome. Sci Transl Med. Aug 29;10(456). DOI: 10.1126/scitranslmed.aam7510
  7. 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.*@ (2016) The aryl hydrocarbon receptor promotes aging phenotypes across species. Sci Rep. Jan 21;6:19618. DOI: 10.1038/srep19618
  8. Maglioni S, Ventura N. (2016) C. elegans as a model organism for human mitochondrial associated disorders. Mitochondrion. Sep;30:117-25. DOI: 10.1016/j.mito.2016.02.003
  9. Schiavi A, Maglioni S, Palikaras K, Shaik A, Strapazzon F, Brinkmann V, Torgovnick A, Castelein N, De Henau S, Braeckman BP, Cecconi F, Tavernarakis N, Ventura N. (2015) Iron-Starvation-Induced Mitophagy Mediates Lifespan Extension upon Mitochondrial Stress in C. elegans. Curr Biol. 25(14):1810-22. DOI: 10.1016/j.cub.2015.05.059
  10. Maglioni S, Arsalan N, Franchi L, Hurd A, Opipari AW, Glick GD, Ventura N. (2015) An automated phenotype-based microscopy screen to identify pro-longevity interventions acting through mitochondria in C. elegans. BBA Bioenergetics. Nov;1847(11):1469-78. DOI: 10.1016/j.bbabio.2015.05.004
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