Mitochondrial Biochemistry and Biology (MitoB&B). Coordinator: Porcelli

Fig. 1: Visualisation of the mitochondrial network and nucleus in human cells using fluorescence probes.

Research themes

1) To define the role of mitochondrial metabolism in modulating tumorigenesis in order to identify new metabolic targets as adjuvant anticancer therapy, with particular interest in ovarian cancer. The main objective of this research is to demonstrate that respiratory chain complex I is a lethality target by identifying the biochemical and molecular mechanisms that are activated by the lack of this enzyme in different tumour models and how these mechanisms modulate the various stages of tumour progression in vitro and in vivo. In addition, the adaptive mechanisms that tumour cells develop following the inhibition of complex I or its genetic ablation are currently being studied.

2) To define the ways in which respiratory complexes organise themselves into dynamic supramolecular structures to adapt to metabolic changes and to cope with severe energy dysfunctions caused by mitochondrial mutations. Interest is particularly focused on the structural and functional relationships between complex I and III under physiological and pathological conditions, the role of oxidative stress and the identification of new therapeutic strategies for the treatment of mitochondrial diseases.

3) Identification of new assembly factors of complex I of the mitochondrial respiratory chain and new interactors of this enzyme, in order to clarify its assembly mechanism.

 For more information see the MitoB&B website (https://site.unibo.it/mitobb/en)

Lab Members

Anna Maria Porcelli, Full Professor

Anna Maria Ghelli, Associate Professor 

Luisa Iommarini, Associate Professor

Manuela Sollazzo, Junior Assistant Professor

Gaia Tioli,  Research Fellow

Luigi D'Angelo,  Research Fellow

Sara Milioni, PhD Student DIMEC 

Iacopo Gherardi, PhD Student

Damiano Paoli,  Research scholarship holder

Internship projects

For available positions please consult the lecturer pages and contact lecturers by e-mail

Prof. Anna Maria Porcelli (https://www.unibo.it/sitoweb/annamaria.porcelli/didattica?tab=tesi)

Prof. Anna Maria Ghelli (https://www.unibo.it/sitoweb/annamaria.ghelli/didattica?tab=tesi)

Prof. Luisa Iommarini (https://www.unibo.it/sitoweb/luisa.iommarini2/didattica?tab=tesi)

Relevant publications

• Aleo SJ, Del Dotto V, Romagnoli M, Fiorini C, Capirossi G, Peron C, Maresca A, Caporali L, Capristo M, Tropeano CV, Zanna C, Ross-Cisneros FN, Sadun AA, Pignataro MG, Giordano C, Fasano C, Cavaliere A, Porcelli AM, Tioli G, Musiani F, Catania A, Lamperti C, Marzoli SB, De Negri A, Cascavilla ML, Battista M, Barboni P, Carbonelli M, Amore G, La Morgia C, Smirnov D, Vasilescu C, Farzeen A, Blickhaeuser B, Prokisch H, Priglinger C, Livonius B, Catarino CB, Klopstock T, Tiranti V, Carelli V, Ghelli AM. Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy. Cell Rep Med. 2024 Jan 17:101383. doi: 10.1016/j.xcrm.2023.101383.
• Kurelac I, Cavina B, Sollazzo M, Miglietta S, Fornasa A, De Luise M, Iorio M, Lama E, Traversa D, Nasiri HR, Ghelli A, Musiani F, Porcelli AM, Iommarini L, Gasparre G. NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors. Open Biol. 2022 Nov;12(11):220198. doi: 10.1098/rsob.220198.
• Sollazzo M, De Luise M, Lemma S, Bressi L, Iorio M, Miglietta S, Milioni S, Kurelac I, Iommarini L, Gasparre G, Porcelli AM. Respiratory Complex I dysfunction in cancer: from a maze of cellular adaptive responses to potential therapeutic strategies. FEBS J. 2021 Oct 4. doi: 10.1111/febs.16218.
• D'Angelo L, Astro E, De Luise M, Kurelac I, Umesh-Ganesh N, Ding S, Fearnley IM, Gasparre G, Zeviani M, Porcelli AM, Fernandez-Vizarra E, Iommarini L. NDUFS3 depletion permits complex I maturation and reveals TMEM126A/OPA7 as an assembly factor binding the ND4-module intermediate. Cell Rep. 2021 Apr 20;35(3):109002. doi: 10.1016/j.celrep.2021.109002.
• Kurelac I, Iommarini L, Vatrinet R, Amato LB, De Luise M, Leone G, Girolimetti G, Umesh Ganesh N, Bridgeman VL, Ombrato L, Columbaro M, Ragazzi M, Gibellini L, Sollazzo M, Feichtinger RG, Vidali S, Baldassarre M, Foriel S, Vidone M, Cossarizza A, Grifoni D, Kofler B, Malanchi I, Porcelli AM, Gasparre G. Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses. Nat Commun. 2019, 10(1):903. doi: 10.1038/s41467-019-08839-1.