Ian James Holt

Ikerbasque Research Professor, Biogipuzkoa Health Research Institute

Ikerbasque Research Professor at IIS Biogipuzkoa.

Research line:

Energy metabolism and human disease - focusing on defects in the DNA of mitochondria that is transmitted exclusively through the maternal line.

Lucille Markey Visiting Fellowship, Royal Society University Research Fellowship, European Union Descartes Prize (Life Sciences), Visiting Professorship - Radboud Excellence Programme.

Previous research experience at Institute of Neurology (UK) Radboud University (The Netherlands), California Institute of Technology (USA), University of Dundee (Scotland) and Medical Research Council (UK).

Doctor in Biochemistry (1989) from University College London.

Argitalpenak

2024

Article / Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation

Brain

Muñoz-Oreja, M.; Sandoval, A.; Bruland, O.; Perez-Rodriguez, D.; Fernandez-Pelayo, U.; Lopez De Arbina, A.; Villar-Fernandez, M.; Hernández-Eguiazu, H.; Hernández, I.; Park, Y.; Goicoechea, L.; Pascual-Frías, N.; Garcia-Ruiz, C.; Fernandez-Checa, J.; Martí-Carrera, I.; Gil-Bea, F.J.; Hasan, M.T.; Gegg, M.E.; Bredrup, C.; Knappskog, P.M.; Gereñu-Lopetegui, G.; Varhaug, K.N.; Bindoff, L.A.; Spinazzola, A.; Yoon, W.H.; Holt, I.J.

Article / Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis

Acta Neuropathologica

Zufiría, M.; Pikatza-Menoio, O.; Garciandia-Arcelus, M.; Bengoetxea, X.; Jiménez, A.; Elicegui, A.; Levchuk, M.; Arnold-García, O.; Ondaro, J.; Iruzubieta, P.; Rodríguez-Gómez, L.; Fernández-Pelayo, U.; Muñoz-Oreja, M.; Aiastui, A.; García-Verdugo, J.M.; Herranz-Pérez, V.; Zulaica, M.; Poza, J.J.; Ruiz-Onandi, R.; Fernández-Torrón, R.; Espinal, J.B.; Bonilla, M.; Lersundi, A.; Fernández-Eulate, G.; Riancho, J.; Vallejo-Illarramendi, A.; Holt, I.J.; Sáenz, A.; Malfatti, E.; Duguez, S.; Blázquez, L.; López de Munain, A.; Gerenu, G.; Gil-Bea, F.; Alonso-Martín, S.

Review / Mitochondrial DNA competition: starving out the mutant genome

Trends in Pharmacological Sciences

Spinazzola, A.; Perez-Rodriguez, D.; Ježek, J.; Holt, I.J.

2022

Article / 2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart

Scientific Reports

Aiestaran-Zelaia, I.; Sánchez-Guisado, M.J.; Villar-Fernandez, M.; Azkargorta, M.; Fadon-Padilla, L.; Fernandez-Pelayo, U.; Perez-Rodriguez, D.; Ramos-Cabrer, P.; Spinazzola, A.; Elortza, F.; Ruíz-Cabello, J.; Holt, I.J.

Review / Defects of Nutrient Signaling and Autophagy in Neurodegeneration

Frontiers in Cell and Developmental Biology

Ondaro, J.; Hernandez-Eguiazu, H.; Garciandia-Arcelus, M.; Loera-Valencia, R.; Rodriguez-Gómez, L.; Jiménez-Zúñiga, A.; Goikolea, J.; Rodriguez-Rodriguez, P.; Ruiz-Martinez, J.; Moreno, F.; Lopez de Munain, A.; Holt, I.J.; Gil-Bea, F.J.; Gereñu, G.

2021

Article / Small molecules couple mitochondrial DNA replication with mitochondrial fitness and promote the selection of wild-type over mutant mitochondrial DNA

Nature Communications

Pantic, B., et al.

Article / 2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness and promotes the selection of wild-type over mutant mitochondrial DNA

Nature Communications

Pantic, B.; Ives, D.; Mennuni, M.; Perez-Rodriguez, D.; Fernandez-Pelayo, U.; Lopez de Arbina, A.; Muñoz-Oreja, M.; Villar-Fernandez, M.; Dang, T.m.J.; Vergani, L.; Johnston, I.G.; Pitceathly, R.D.S.; McFarland, R.; Hanna, M.G.; Taylor, R.W.; Holt, I.J.; Spinazzola, A.

Article / Uniparental isodisomy of chromosome 2 causing MRPL44-related multisystem mitochondrial disease

Molecular Biology Reports

Horga, A.; Manole, A.; Mitchell, A.L.; Bugiardini, E.; Hargreaves, I.P.; Mowafi, W.; Bettencourt, C.; Blakely, E.L.; He, L.; Polke, J.M.; Woodward, C.E.; Dalla Rosa, I.; Shah, S.; Pittman, A.M.; Quinlivan, R.; Reilly, M.M.; Taylor, R.W.; Holt, I.J.; Hanna, M.G.; Pitceathly, R.D.S.; Spinazzola, A.; Houlden, H.

2020

Article / Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism

American Journal of Human Genetics

Gunning, A.C.; Strucinska, K.; Muñoz Oreja, M.; Parrish, A.; Caswell, R.; Stals, K.L.; Durigon, R.; Durlacher-Betzer, K.; Cunningham, M.H.; Grochowski, C.M.; Baptista, J.; Tysoe, C.; Baple, E.; Lahiri, N.; Homfray, T.; Scurr, I.; Armstrong, C.; Dean, J.; Fernandez Pelayo, U.; Jones, A.W.E.; Taylor, R.W.; Misra, V.K.; Yoon, W.H.; Wright, C.F.; Lupski, J.R.; Spinazzola, A.; Harel, T.; Holt, I.J.; Ellard, S.

2019

Article / Parkinsonism and spastic paraplegia type 7: Expanding the spectrum of mitochondrial Parkinsonism

Movement Disorders

De la Casa-Fages, B.; Fernández-Eulate, G.; Gamez, J.; Barahona-Hernando, R.; Morís, G.; García-Barcina, M.; Infante, J.; Zulaica, M.; Fernández-Pelayo, U.; Muñoz-Oreja, M.; Urtasun, M.; Olaskoaga, A.; Zelaya, V.; Jericó, I.; Saez-Villaverde, R.; Catalina, I.; Sola, E.; Martínez-Sáez, E.; Pujol, A.; Ruiz, M.; Schlüter, A.; Spinazzola, A.; Muñoz-Blanco, J.L.; Grandas, F.; Holt, I.; Álvarez, V.; López de Munaín, A.

Article / MRPS25 mutations impair mitochondrial translation and cause encephalomyopathy

Human Molecular Genetics

Bugiardini, E.; Mitchell, A.L.; Rosa, I.D.; Horning-Do, H.T.; Pitmann, A.M.; Poole, O.V.; Holton, J.L.; Shah, S.; Woodward, C.; Hargreaves, I.; Quinlivan, R.; Amunts, A.; Wiesner, R.J.; Houlden, H.; Holt, I.J.; Hanna, M.G.; Pitceathly, R.D.S.; Spinazzola, A.

Article / Survey and summary: The mitochondrial R-loop

Nucleic Acids Research

Holt, I.J.

Letter / Reply to: “Mitochondrial Parkinsonism due to SPG7/Paraplegin variants with secondary mtDNA depletion”

Movement Disorders

Review / The Jekyll and Hyde character of RNase H1 and its multiple roles in mitochondrial DNA metabolism

DNA Repair

Holt, I.J.

2018

Article / LETM1 couples mitochondrial DNA metabolism and nutrient preference

EMBO Molecular Medicine

Durigon, R.; Mitchell, A.L.; Jones, A.W.E.; Manole, A.; Mennuni, M.; Hirst, E.M.A.; Houlden, H.; Maragni, G.; Lattante, S.; Doronzio, P.N.; Dalla Rosa, I.; Zollino, M.; Holt, I.J.; Spinazzola, A.

Article / Transcript availability dictates the balance between strand-asynchronous and strand-coupled mitochondrial DNA replication

Nucleic Acids Research

Cluett, T.J.; Akman, G.; Reyes, A.; Kazak, L.; Mitchell, A.; Wood, S.R.; Spinazzola, A.; Spelbrink, J.N.; Holt, I.J.

2017

Article / Aberrant ribonucleotide incorporation and multiple deletions in mitochondrial DNA of the murine MPV17 disease model

Nucleic Acids Research

Moss, C.F.; Rosa, I.D.; Hunt, L.E.; Yasukawa, T.; Young, R.; Jones, A.W.E.; Reddy, K.; Desai, R.; Virtue, S.; Elgar, G.; Voshol, P.; Taylor, M.S.; Holt, I.J.; Reijns, M.A.M.; Spinazzola, A.

Letter / Reply: Genotype-phenotype correlation in ATAD3A deletions: Not just of scientific relevance

Brain

Frazier, A.E.; Holt, I.J.; Spinazzola, A.; Thorburn, D.R.