Determinants of mitochondrial physiology and intercellular transfer in the nervous system

Research

Our work seeks to unravel the mechanisms that underlie a wide variety of neurological disorders, in particular neurodegenerative and oncogenic, which have in common an alteration of mitochondrial function. To explore how they occur, we study the interplay between the morphology, ultrastructure, and dynamics of these organelles in the regulation of metabolism, respiration, redox status, and neural bioenergetics.

We focus our main interest on the coordination of the function of mitochondria between cells and tissues, through intercellular transfer of mitochondrial content.

Lines of investigation

1) Mitochondrial dynamics, metabolism and bioenergetics

2) Intercellular communication and mitochondrial exchange

3) Mitochondrial transfer and morphofunctional reconfiguration

Team

Publications of the last years

• Aberrant upregulation of the glycolytic enzyme PFKFB3 in CLN7 neuronal ceroid lipofuscinosis.
  Lopez-Fabuel I, Garcia-Macia M, Buondelmonte C, Burmistrova O, Bonora N, Alonso-Batan P, Morant-Ferrando B, Vicente-Gutierrez C, Jimenez-Blasco D, Quintana-Cabrera R, Fernández E, Llop J, Ramos-Cabrer P, Sharaireh A, Guevara-Ferrer M, Fitzpatrick L, Thompton C, McKay T, Storch S, Medina D, Mole S, Fedichev P, Almeida A, and Bolaños JP.
  NATURE COMUNICATIONS Jan 27;13(1):536 (2021)
  DOI: 10.1038/s41467-022-28191-1
• Opa1 relies on cristae preservation and ATP synthase to curtail reactive oxygen species accumulation in mitochondria
  T2. Quintana-Cabrera R*, Manjarrés-Raza I, Vicente-Gutiérrez C, Corrado M, Bolaños JP, Scorrano, L* (*Autor de co correspondencia).
  REDOX BIOLOGY March 19;41:101944 (2021)
  DOI: 10.1016/j.redox.2021.101944
• Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy
  Zaninello M. Dr. Konstantinos Palikaras , Dr. Deborah Naon , Dr. Keiko Iwata , Dr. Stéphanie Herkenne , Dr. Ruben Quintana-Cabrera , Dr. Martina Semenzato , Dr. Francesca Grespi , Mr. Fred Ross-Cisneros , Dr. Valerio Carelli , Prof. Alfredo Sadun , Prof. Nektarios Tavernarakis, Luca Scorrano
  NATURE COMUNICATIONS Aug 12; 11(1):4029 (2020)
  DOI: 10.1038/s41467-020-17821-1
• Intertwined ROS and Metabolic Signaling at the Neuron-Astrocyte Interface
  Vicente-Gutiérrez C, Jiménez-Blasco D, Quintana-Cabrera R.
  NEUROCHEMICAL RESEARCH Jan 27 (2020)
  DOI: 10.1007/s11064-020-02965-9
• ER stress priming of mitochondrial respiratory suPERKomplex assembly
  Quintana-Cabrera, R., Soriano, M.E
  TRENDS IN ENDOCRINOLOGY & METABOLISM Aug 24 (2019)
  DOI: doi: 10.1016/j.tem.2019.08.003.
• Impaired Mitochondrial ATP Production Downregulates Wnt Signaling via ER Stress Induction.
  6. Costa R, Peruzzo R, Bachmann M, Montà GD, Vicario M, Santinon G, Mattarei A, Moro E, Quintana-Cabrera R, Scorrano L, Zeviani M, Vallese F, Zoratti M, Paradisi C, Argenton F, Brini M, Calì T, Dupont S, Szabò I, Leanza L.
  CELL REPORTS Aug 20;28(8):1949-1960.e6. (2019)
  DOI: 10.1016/j.celrep.2019.07.050
• PARP inhibitor PJ34 protects mitochondria and induces DNA-damage mediated apoptosis in combination with cisplatin or temozolomide in B16F10 melanoma cells.
  Cseh A, Fábián Z, Quintana-Cabrera R ,Szabó A, Erős K, Soriano ME, Gallyas F, Scorrano L, Sümegi B.
  FRONTIERS IN PHYSIOLOGY May 7;10:538 eCollection (2019)
  DOI: 10.3389/fphys.2019.00538
• MFN2 mutations in Charcot-Marie-Tooth disease alter mitochondria-associated ER membrane function but do not impair bioenergetics.
  8. Larrea D, Pera M, Gonelli A, Quintana-Cabrera R, Akman HO, Guardia-Laguarta C, Velasco KR, Area-Gomez E, Dal Bello F, De Stefani D, Horvath R, Shy ME, Schon EA, Giacomello M.
  HUMAN MOLECULAR GENETICS Jan 11 (2019)
  DOI: 10.1093/hmg/ddz008
• The cristae modulator Optic atrophy 1 requires mitochondrial ATP synthase oligomers to safeguard mitochondrial function.
  Quintana-Cabrera, R, Quirin C, Glytsou C, Corrado M, Urbani A, Pellattiero A, Calvo E, Vázquez J, Enríquez JA, Gerle C, Soriano ME, Bernardi P, Scorrano L.
  NATURE COMMUNICATIONS Aug 24 (2018)
  DOI: 10.1038/s41467-018-05655-x
• Who and how in the regulation of mitochondrial cristae shape and function.
  Quintana-Cabrera R, Mehrotra A, Rigoni G, Soriano ME
  BIOCHEM BIOPHYS RES COMMUN Apr 21. pii: S0006-291X(17)30763-5 (2017)
  DOI: 0.1016/j.bbrc.2017.04.088
• (Neuro)degenerated Mitochondria-ER contacts.
  De Mario A, Quintana-Cabrera R, Martinvalet D, Giacomello M.
  BIOCHEM BIOPHYS RES COMMUN Feb 19; 483(4):1096-1109. Special Issue: Neurodegeneration. Volume 483, Issue 4, Pages 979-1194 (19 February 2017) (2017)
  DOI: 10.1503/jpn.150209
• Early effects of the anti-neoplastic agent salinomycin on mitochondrial function.
  12. Managò A., Leanza L., Carraretto L., Sassi N., Grancara S., Quintana-Cabrera R., Trimarco V., Toninello A., Scorrano L., Trentin L., Gulbins E., Zoratti M., Szabò I.
  CELL DEATH DIS Oct 22; 6:e1930 (2015)
  DOI: 10.1038/cddis.2015.263
• Controlled overexpression of the mitochondria shaping protein Optic Atrophy 1 counteracts cellular damage in vivo.
  Varanita T., Soriano M.E., Romanello V., Zaglia T., Quintana-Cabrera R., Semenzato M., Menabò R., Costa V., Civiletto G., Pesce P., Viscomi C., Zeviani M., Di Lisa F., Mongillo M., Sandri M., Scorrano L.
  CELL METABOLISM Jun 2;21(6):834-442T2T (2015)
• Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency.
  ogliati S.; Frezza C.; Soriano ME.; Varanita T.; Quintana-Cabrera R.; Corrado M.; Cipolat S., Costa V., Casarin A., Gomes LC., Perales-Clemente E.; Salviati L.; Fernandez-Silva P.; Enriquez JA.; Scorrano L.
  CELL Sep 26;155(1):160-71. (2013)
  DOI: 10.1016/j.cell.2013.08.032
• Glutathione and γ-glutamylcysteine in hydrogen peroxide detoxification.
  Quintana-Cabrera R., Bolaños JP.
  METHODS IN ENZYMOLOGY 527:129-44. Special Issue: Hydrogen Peroxide and cell signaling, Part B. Volume 527, Pages 2-321 (2013). Edited by Enrique Cadenas and Lester Packer (2013)
  DOI: 10.1016/B978-0-12-405882-8.00007-6.
• Glutathione and γ-glutamylcysteine in the antioxidant and survival functions of mitochondria.
  Quintana-Cabrera R., Bolaños JP
  BIOCHEM. SOC. TRANS.; Feb 1;41(1):106-10 (2013)
  DOI: 10.1042/BST20120252
• siRNA knock down of glutamate dehydrogenase in astrocytes affects glutamate metabolism leading to extensive accumulation of the neuroactive amino acids glutamate and aspartate.
  Skytt DM; Klawonn AM; Stridh MH; Pajecka K; Patruss Y; Quintana-Cabrera, R.; Bolaños JP; Schousboe A.; Waagepetersen HS.
  NEUROCHEMISTRY INTERNATIONAL Sep;61(4):490-7 (2012)
  DOI: 10.1016/j.neuint.2012.04.014
• γ-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor
  Quintana-Cabrera, R.; Fernandez-Fernandez, S.; Bobo-Jimenez, V.; Escobar, J.; Sastre, J; Almeida, A.; Bolaños, J.P.
  NATURE COMMUNICATIONS Mar 6;3:718 (2012)
  DOI: DOI: 10.1038/ncomms1722

Contact

Others