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

Research themes

The main research topics are:

1) Defining the role of mitochondrial metabolism in the modulation of tumorigenesis in order to identify new metabolic targets as adjuvant anticancer therapy, with particular interest in ovarian cancer. In particular, the main objective of this research topic is to demonstrate that respiratory complex I is a target of lethality by identifying the biochemical and molecular mechanisms that are activated by the lack of this enzyme in different tumor models and to investigate how these mechanisms modulate the various steps of tumor progression in in vitro and in vivo models. In addition, the adaptive mechanisms that tumor cells develop following pharmacological inhibition of complex I or its genetic ablation are currently under investigation.

2) To define the ways in which respiratory complexes organize into dynamic supra-molecular structures to adapt to metabolic changes and to cope with severe energy dysfunction caused by mitochondrial mutations. The interest is directed in particular to the structural and functional relationships between complex I and III in physiological and pathological conditions, to the role of oxidative stress and to 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 the mechanism of its assembly.

Lab members

Prof. ssa Anna Maria Porcelli,  Associate Professor (https://www.unibo.it/sitoweb/annamaria.porcelli)

Prof. ssa Anna Maria Ghelli, Associate Professor (https://www.unibo.it/sitoweb/annamaria.ghelli)

Prof. ssa Luisa Iommarini, Associate Professor (https://www.unibo.it/sitoweb/luisa.iommarini2)

Dott. Manuela Sollazzo, research fellow (https://www.unibo.it/sitoweb/manuela.sollazzo2/)

Stefano Miglietta,  fellowship

Dott.ssa Gaia Tioli, research fellow (https://www.unibo.it/sitoweb/gaia.tioli2/)

Luigi D'Angelo, PhD student (https://www.unibo.it/sitoweb/luigi.dangelo4)

Sara Milioni, PhD student (https://www.unibo.it/sitoweb/sara.milioni2)

Internship projects

https://www.unibo.it/sitoweb/annamaria.porcelli/didattica?tab=tesi

https://www.unibo.it/sitoweb/annamaria.ghelli/didattica?tab=tesi

https://www.unibo.it/sitoweb/luisa.iommarini2/didattica?tab=tesi

Relevant publications

• 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.
• Páleníková P, Harbour ME, Prodi F, Minczuk M, Zeviani M, Ghelli A, Fernández-Vizarra E. Duplexing complexome profiling with SILAC to study human respiratory chain assembly defects. Biochim Biophys Acta Bioenerg. 2021 Jun 1;1862(6):148395. doi: 10.1016/j.bbabio.2021.148395.
• Abla H, Sollazzo M, Gasparre G, Iommarini L, Porcelli AM. The multifaceted contribution of α-ketoglutarate to tumor progression: An opportunity to exploit? Semin Cell Dev Biol. 2020 Feb;98:26-33. doi: 10.1016/j.semcdb.2019.05.031.
• 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.