1-We have published the characterization of a mouse model for the combined OXPHOS dysfunction due to mutations in GFM1 (Molina-Berenguer et al, FASEB J 2022). We have used this model to test an AAV-based gene therapy which has demonstrated to prevent the HEPATIC phenotype in mice. 2-We have published our finding that the protein NDUFA10, a subunit of the mitochondrial OXPHOS Complex I, tightly binds most mitochondrial dGTP (Molina-Granada et al, Commun Biol, 2022). Given the important role of dNTPs in mitochondrial diseases, this novel physiological trait will be important to better understand the pathomechanisms of these disorders. 3- In Villarreal-Salazar et al (Mol Metab, 2022) we have confirmed very poor VO2peak values and impaired muscle glycolytic flux in McArdle disease patients, and found that their severe muscle oxidative capacity impairment could be explained by a mitochondrial network disruption, at least in those fibres with a higher capacity for glycogen accumulation.

Group Leader
Ramon Martí Seves

Principal Investigator (PI)
Elena García-Arumí, Tomàs Pinós Figueras, Yolanda Cámara Navarro

PhD Students
Miguel Molina Berenguer, Javier Ramón Pasías, Mónica Azucena Villareal Salazar, Andrea Férriz Gordillo, Pau Mollá Zaragozá

Lab Technicians
María Jesús Melià Grimal, Antoni Ruíz Vicaría










Molina-Berenguer M, Vila-Julia F, Perez-Ramos S, Salcedo-Allende MT, Camara Y, Torres-Torronteras J, Marti R
Dysfunctional mitochondrial translation and combined oxidative phosphorylation deficiency in a mouse model of hepatoencephalopathy due to Gfm1 mutations
FASEB J. 2022 Jan;36(1):e22091
DOI: doi: 10.1096/fj.202100819RRR
IF: 5.191

Molina-Granada D, Gonzalez-Vioque E, Dibley MG, Cabrera-Perez R, Vallbona-Garcia A, Torres-Torronteras J, Sazanov LA, Ryan MT, Camara Y, Marti R
Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit
Commun Biol. 2022 Jun 23;5(1):620
DOI: doi: 10.1038/s42003-022-03568-6.
IF: 6.548

Villarreal-Salazar M, Santalla A, Real-Martinez A, Nogales-Gadea G, Valenzuela PL, Fiuza-Luces C, Andreu AL, Rodriguez-Aguilera J, Martin MA, Arenas J, Vissing J, Lucia A, Krag TO, Pinos T
Low aerobic capacity in McArdle disease: a role for mitochondrial network impairment?
Mol Metab. 2022 Dec;66:101648
DOI: doi: 10.1016/j.molmet.2022.101648
IF: 8.568

Shintaku J, Pernice WM, Eyaid W, Gc JB, Brown ZP, Juanola-Falgarona M, Torres-Torronteras J, Sommerville EW, Hellebrekers DM, Blakely EL, Donaldson A, van de Laar IM, Leu CS, Marti R, Frank J, Tanji K, Koolen DA, Rodenburg RJ, Chinnery PF, Smeets HJM, Gorman GS, Bonnen PE, Taylor RW, Hirano M
RRM1 variants cause a mitochondrial DNA maintenance disorder via impaired de novo nucleotide synthesis
J Clin Invest. 2022 Jul 1;132(13). pii: 145660
DOI: doi: 10.1172/JCI145660
IF: 19.477

Keraite I, Becker P, Canevazzi D, Frias-Lopez C, Dabad M, Tonda-Hernandez R, Paramonov I, Ingham MJ, Brun-Heath I, Leno J, Abuli A, Garcia-Arumi E, Heath SC, Gut M, Gut IG
A method for multiplexed full-length single-molecule sequencing of the human mitochondrial genome
Nat Commun. 2022 Oct 6;13(1):5902
DOI: doi: 10.1038/s41467-022-33530-3
IF: 17.694

Preclinical efficacy studies for the use of deoxyribonucleosides as a treatment for mitochondrial DNA depletion/multiple deletions syndromes (MDDS). Extension to unexplored genetic cause
Principal Investigator: Ramon Martí
Agency: Instituto de Salud Carlos III (Ref. PI21/00554)
Funding: 153,670 €
Period: January 2022 – December 2024

Deoxyribonucleosides as a therapy for mitochondrial DNA replication disorders: understanding therapeutic mechanisms and broadening the treatment to mutations in POLG and other related genes
Principal Investigator: Ramon Martí
Agency: Fundació La Marató de TV3
Funding: 296,375 €
Period: May 2021 – April 2024

Acciones para mejorar la calidad de vida de los pacientes de McArdle: una aproximación multidisciplinaria
Principal Investigator: Tomàs Pinós
Agency: Instituto de Salud Carlos III (Ref. PI19/01313)
Funding: 123,420 €
Period: January 2020 – December 2022

Mitochondrial respiratory complex I at the interface between oxidative metabolism and nucleotide homeostasis
Principal Investigator: Yolanda Cámara
Agency: Ministerio de Ciencia e Innovación «Proyectos I+D+i» 2020 - Modalidad «Retos Investigación» (Ref. PID2020-112929RB-I00)
Funding: 157,300 €
Period: Sep 2021-Aug 2024

Desarrollo de una estrategia de terapia génica para la deficiencia combinada de la fosforilación oxidativa tipo 1 debido a mutaciones en GFM1
Principal Investigator: Ramon Martí
Agency: Fundación Mutua Madrileña
Funding: 150,000 €
Period: July 2021 – June 2024

Deoxynucleoside substrate enhancement therapy for thymidine kinase 2 (TK2) deficiency
Priority Number: US201562180914P
Priority Date: 17/06/2015

Treatment of Mitochondrial Diseases
Priority Number: EP15170825.2
Priority Date: 05/06/2015
Applicants: 70% VHIR; 30% CIBERER