Prof. Ian James Holt

My graduate studies launched the molecular era of human mitochondrial diseases, and led to a life-long fascination with the DNA in mitochondria. Having experienced such a breakthrough early in my career, I believe there is no limit to what can be achieved as a graduate student.

Prof. Ian James Holt is a Ikerbasque Research Professor and Leader of the Mitochondria, Health and Longevity Group at the Biodonostia Health Research Institute, Neurosciences department, San Sebastián, Spain.

Prof. Holt is a leader in the field of energy production and human disease with a special focus on the DNA in mitochondria. The overarching aim of his Research Group is to understand the contribution of altered energy metabolism to a range of human diseases. The allied goal is to use this knowledge to design interventions to slow or arrest the decline in energy metabolism and thereby extend human health and lifespan. A central component of the Group´s approach is to dissect how nutrient availability affects mitochondrial DNA metabolism and vice-versa. Recent advances by his group in this field have identified new therapeutic strategies for mitochondrial DNA disorders, which also have the potential to slow the progressive decline in mitochondrial function that is a feature of many neurodegenerative disorders and is a hallmark of ageing.

Prof. Holt is supervising DC7 and DC11 and co-supervising DC2 and DC10.

Accordion Content
  • Aiestaran-Zelaia I., Sánchez-Guisado M.J., et al. (2022), 2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart. Sci Rep. 12(1):6890. Holt I. was lead investigator of the study and co-supervisor of the first two authors who are current PhD students. DOI
  • Pantic, B., Ives, D., Mennuni, M., et al. (2021), 2-Deoxy-D-glucose couples mitochondrial DNA replication with mitochondrial fitness and promotes the selection of wild-type over mutant mitochondrial DNA. Nat Commun 12, 6997. Holt I. was co-lead investigator and (co-)supervisor o the two graduate students. DOI
  • Gunning A.C., Strucinska K., Muñoz Oreja M., et al. (2020), Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism. Am J Hum Genet. 6;106(2):272-279. Holt. I. was a lead investigator and supervisor of Muñoz M. DOI
  • Desai R., et al. (2017), ATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism. Brain, 140 (6), 1595–1610. Holt I. was a lead investigator and supervisor of the first author. DOI
  • Cluett T.J., et al. (2018), Transcript availability dictates the balance between strand-asynchronous and strand-coupled mitochondrial DNA replication. Nucleic Acids Res. 46(20):10771-10781. Holt I. was lead investigator and supervisor of the first author graduate student. DOI
  • Akman G., et al. (2016), Pathological ribonuclease H1 causes R-loop depletion and aberrant DNA segregation in mitochondria. Proc Natl Acad Sci 113 (30) E4276-E4285. Holt I. was the lead investigator and supervisor of the first author. DOI
  • Moss. C.F., et al. (2017), Aberrant ribonucleotide incorporation and multiple deletions in mitochondrial DNA of the murine MPV17 disease model. Nucleic Acids Res. 45 (22), 12808–12815. Holt I. was a lead investigator and supervisor of the first author PhD student. DOI

Prof. Ian Holt graduated from Newcastle University (Newcastle-upon-Tyne, UK) and obtained his PhD at the Institute of Neurology, University College London. He discovered the first genetic cause of human mitochondrial disease (deletions in mitochondrial DNA) and was the first to show that the nucleus controls the selection of mitochondrial DNA variants in human cells. Recently, with Prof. Spinazzola, he has identified small molecules that purge cells of mutant mitochondrial DNA and outlined their mechanism of action. During 16 years as a program leader at the British Medical Research Council, Ian Holt defined key features of mitochondrial DNA replication, including new mechanisms. He joined the Biodonostia Research Institute as an Ikerbasque Research Professor, and Leader of the Mitochondria, Health and Longevity Group. He maintains strong collaborations with University College London and has forged new collaborations in the Basque country that enable the group to study the patho-physiological consequences of altered mitochondrial function. His research is currently funded by the Carlos III Health Institute, the Basque Government Ministries of Health and Economy and Competitiveness and the European Union. He is currently directing 4 doctoral theses, having supervised another 19 doctoral students to the successful completion of their PhD.