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MRC Mitochondrial Biology Unit



  Michal Minczuk

  MRC Investigator




Mitochondrial genetics: Mitochondrial genome engineering to unravel the genetic links between mitochondrial gene regulation and human disease for future therapies

In eukaryotic organisms almost all genetic information is encoded in DNA present in the nucleus of the cell, but a small DNA molecule inhabits mitochondria, cellular structures that provide energy from food for the cells to use. Mitochondrial DNA contains genes that are vital for the physiological functioning of the cell, and genetic defects causing dysfunction of mitochondrial DNA can lead to human diseases. We still do not know how mitochondrial genes work exactly.One of the ways to investigate the role of a gene, or to discover its biological function, it to change or disrupt DNA, and then to look for the effect on cultured cells, or on the whole organism. These methods of genetic modification are often powerful ways of studying disease genes encoded in the nucleus, but they cannot be applied to mammalian mitochondrial DNA. Also, many genes regulating mitochondrial function are still unknown. Therefore, our research goals are to identify new genes regulating mitochondria, define how these mitochondrial genes operate and to provide the technology to allow mammalian mitochondrial DNA to be modified genetically. It could be an invaluable way of understanding mitochondrial diseases and for advancing the quest for therapies.


Michal obtained a Master’s degree in Biotechnology (1999) and PhD in Biological Sciences (2003) from the University of Warsaw, Poland, carrying out research in the Institute of Genetics and Biotechnology. From 2004–2007 he was an FEBS Postdoctoral Fellow in the group of Aaron Klug at Medical Research Council (MRC), Laboratory of Molecular Biology, Cambridge. Michal joined the MRC Mitochondrial Biology Unit as an Investigator Scientist (2007) and in 2009 he became a MRC Investigator. Throughout his career Michal has received numerous awards and personal fellowships, including the Prime Minister Prize for his PhD thesis, Award of the Foundation for Polish Science, EMBO and FEBS Fellowships, served as an editor of several journals and books and organised a number of scientific conferences. More recently, Michal has co-founded Pretzel Therapeutics, a start-up biotechnology company that focuses on the development of therapies to treat unmet needs in diseases driven by mitochondrial dysfunction.


Selected Publications

Desai N, Yang H, Chandrasekaran V, Kazi R, Minczuk M & Ramakrishnan V (2020)
Elongational stalling activates mitoribosome-associated quality control.
Science 370, 1105 - 1110

Gammage PA, Viscomi C, Simard M-L, Costa ASH, Gaude E, Powell CA, Van Haute L, McCann BJ, Rebelo-Guiomar P, Cerutti R, Zhang L, Rebar EJ, Zeviani M, Frezza C, Stewart JB & Minczuk M (2018)
Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo.
Nat Med 24, 1691-1695

Pearce SF, Rorbach J, Van Haute L, D'Souza AR, Rebelo-Guiomar P, Powell CA, Brierley I, Firth AE & Minczuk M (2017)
Maturation of selected human mitochondrial tRNAs requires deadenylation.
eLife 6, e27596

Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, Powell CA, Rorbach J, Lantaff R, Blanco S, Sauer S, Kotzaeridou U, Hoffmann GF, Memari Y, Kolb-Kokocinski A, Durbin R, Mayr JA, Frye M, Prokisch H & Minczuk M (2016)
Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3.
Nat Commun 7, 12039

Powell CA, Kopajtich R, D'Souza AR, Rorbach J, Kremer LS, Husain RA, Dallabona C, Donnini C, Alston CL, Griffin H, Pyle A, Chinnery PF, Strom TM, Meitinger T, Rodenburg RJ, Schottmann G, Schuelke M, Romain N, Haller RG, Ferrero I, Haack TB, Taylor RW, Prokisch H & Minczuk M (2015)
TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies.
Am J Hum Genet 97, 319-28

Kornblum C, Nicholls TJ, Haack TB, Schöler S, Peeva V, Danhauser K, Hallmann K, Zsurka G, Rorbach J, Iuso A, Wieland T, Sciacco M, Ronchi D, Comi GP, Moggio M, Quinzii CM, DiMauro S, Calvo SE, Mootha VK, Klopstock T, Strom TM, Meitinger T, Minczuk M*, Kunz WS* & Prokisch H (2013)
Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease.
Nat Genet 45, 214-9

Publication profile - Google Scholar

PubMed (last 10 years)

Group Members

   Christopher Powell
   Lindsey van Haute
   Pedro Guiomar
   Pedro Pinheiro
   Petra Palenikova
   Timo Rey
Post-graduate students
   Lucia Luengo Gutierrez
   Christian Mutti
   Pavel Nash



Tel: +44(0)1223 252700