Joanna Rorbach group

Mitochondrial dysfunction is a major contributor to metabolic and neurodegenerative pathologies, ageing and cancer. Indeed, several key factors regulating mitochondrial gene expression are associated with a range of human diseases. The objective of our research is to better understand the post-transcriptional regulatory networks controlling gene expression in mitochondria; as a means to identify pathways and factors impinging upon physiology and disease.

Research interest

Mammalian mitochondrial ribosomes synthesise a small subset of proteins that are important components of the oxidative phosphorylation machinery, therefore their function is of fundamental importance to cellular metabolism, viability and function.

Most studies of ribosome assembly and function have been carried out on bacterial and eukaryotic cytosolic ribosomes, which differ substantially from mammalian mitoribosomes both compositionally and mechanistically. At present, very little is known about the assembly pathways of mitoribosomes and their regulation. Moreover, many fundamental questions concerning the mechanistic aspects of mitochondrial protein synthesis remain. For example, we do not understand how the nascent protein products of translational machinery are inserted into the inner membrane of mammalian mitochondria.

Our research is directed towards overcoming this knowledge gap, providing a detailed description of mitochondrial ribosome biogenesis, membrane interaction, and structural and biochemical characterisation of different stages of protein synthesis. We employ highly multidisciplinary approaches to address these questions, including ribosome profiling, high-throughput gene targeting, proteomic and cryo-EM methods.

This studies will help us to identify novel factors, some of which may be implicated in disease. In longer term, a description of these processes will yield valuable insight into how the mitochondrial gene expression is regulated, how and why errors occur, and how this impinges upon cellular function and leads to disease.

For more detailed information about our group, visit Rorbach Lab.

Work opportunities

We offer master student, PhD and Postdoc positions to highly motivated and enthusiastic researchers. For details, send an email to



Mechanism of mitoribosomal small subunit biogenesis and preinitiation.
Itoh Y, Khawaja A, Laptev I, Cipullo M, Atanassov I, Sergiev P, Rorbach J, Amunts A
Nature 2022 06;606(7914):603-608

Impaired plasma cell differentiation associates with increased oxidative metabolism in IκBNS-deficient B cells.
Erikson E, Ádori M, Khoenkhoen S, Zhang J, Rorbach J, Castro Dopico X, Karlsson Hedestam G
Cell Immunol 2022 05;375():104516

Structural basis for late maturation steps of the human mitoribosomal large subunit.
Cipullo M, Gesé GV, Khawaja A, Hällberg BM, Rorbach J
Nat Commun 2021 06;12(1):3673

YbeY is required for ribosome small subunit assembly and tRNA processing in human mitochondria.
D'Souza AR, Van Haute L, Powell CA, Mutti CD, Páleníková P, Rebelo-Guiomar P, Rorbach J, Minczuk M
Nucleic Acids Res 2021 06;49(10):5798-5812

Seropositivity in blood donors and pregnant women during the first year of SARS-CoV-2 transmission in Stockholm, Sweden.
Castro Dopico X, Muschiol S, Christian M, Hanke L, Sheward DJ, Grinberg NF, Rorbach J, Bogdanovic G, Mcinerney GM, Allander T, Wallace C, Murrell B, Albert J, Karlsson Hedestam GB
J Intern Med 2021 09;290(3):666-676

Aberrant splicing in neuroblastoma generates RNA-fusion transcripts and provides vulnerability to spliceosome inhibitors.
Shi Y, Yuan J, Rraklli V, Maxymovitz E, Cipullo M, Liu M, Li S, Westerlund I, Bedoya-Reina OC, Bullova P, Rorbach J, Juhlin CC, Stenman A, Larsson C, Kogner P, O'Sullivan MJ, Schlisio S, Holmberg J
Nucleic Acids Res 2021 03;49(5):2509-2521

Human GTPBP5 is involved in the late stage of mitoribosome large subunit assembly.
Cipullo M, Pearce SF, Lopez Sanchez IG, Gopalakrishna S, Krüger A, Schober F, Busch JD, Li X, Wredenberg A, Atanassov I, Rorbach J
Nucleic Acids Res 2021 01;49(1):354-370

Human Mitoribosome Biogenesis and Its Emerging Links to Disease.
Lopez Sanchez MIG, Krüger A, Shiriaev DI, Liu Y, Rorbach J
Int J Mol Sci 2021 Apr;22(8):

Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth.
Sighel D, Notarangelo M, Aibara S, Re A, Ricci G, Guida M, Soldano A, Adami V, Ambrosini C, Broso F, Rosatti EF, Longhi S, Buccarelli M, D'Alessandris QG, Giannetti S, Pacioni S, Ricci-Vitiani L, Rorbach J, Pallini R, Roulland S, Amunts A, Mancini I, Modelska A, Quattrone A
Cell Rep 2021 Apr;35(4):109024

Mitoribosome Profiling from Human Cell Culture: A High Resolution View of Mitochondrial Translation.
Pearce SF, Cipullo M, Chung B, Brierley I, Rorbach J
Methods Mol Biol 2021 ;2192():183-196

Quantitative density gradient analysis by mass spectrometry (qDGMS) and complexome profiling analysis (ComPrAn) R package for the study of macromolecular complexes.
Páleníková P, Harbour ME, Ding S, Fearnley IM, Van Haute L, Rorbach J, Scavetta R, Minczuk M, Rebelo-Guiomar P
Biochim Biophys Acta Bioenerg 2021 Jun;1862(6):148399

Differential processing and localization of human Nocturnin controls metabolism of mRNA and nicotinamide adenine dinucleotide cofactors.
Abshire ET, Hughes KL, Diao R, Pearce S, Gopalakrishna S, Trievel RC, Rorbach J, Freddolino PL, Goldstrohm AC
J Biol Chem 2020 10;295(44):15112-15133

Methylation of Ribosomal RNA: A Mitochondrial Perspective.
Lopez Sanchez MIG, Cipullo M, Gopalakrishna S, Khawaja A, Rorbach J
Front Genet 2020 ;11():761

Distinct pre-initiation steps in human mitochondrial translation.
Khawaja A, Itoh Y, Remes C, Spåhr H, Yukhnovets O, Höfig H, et al
Nat Commun 2020 06;11(1):2932

MitoRibo-Tag Mice Provide a Tool for In Vivo Studies of Mitoribosome Composition.
Busch JD, Cipullo M, Atanassov I, Bratic A, Silva Ramos E, Schöndorf T, et al
Cell Rep 2019 Nov;29(6):1728-1738.e9

C6orf203 is an RNA-binding protein involved in mitochondrial protein synthesis.
Gopalakrishna S, Pearce SF, Dinan AM, Schober FA, Cipullo M, Spåhr H, et al
Nucleic Acids Res. 2019 09;47(17):9386-9399

Myosin VI-Dependent Actin Cages Encapsulate Parkin-Positive Damaged Mitochondria.
Kruppa AJ, Kishi-Itakura C, Masters TA, Rorbach JE, Grice GL, Kendrick-Jones J, et al
Dev. Cell 2018 02;44(4):484-499.e6

Structures of the human mitochondrial ribosome in native states of assembly.
Brown A, Rathore S, Kimanius D, Aibara S, Bai XC, Rorbach J, et al
Nat. Struct. Mol. Biol. 2017 Oct;24(10):866-869

Human mitochondrial ribosomes can switch structural tRNAs - but when and why?
Chrzanowska-Lightowlers Z, Rorbach J, Minczuk M
RNA Biol 2017 12;14(12):1668-1671

Maturation of selected human mitochondrial tRNAs requires deadenylation.
Pearce S, Rorbach J, Van Haute L, D'Souza A, Rebelo-Guiomar P, Powell C, et al
Elife 2017 07;6():

The human RNA-binding protein RBFA promotes the maturation of the mitochondrial ribosome.
Rozanska A, Richter-Dennerlein R, Rorbach J, Gao F, Lewis R, Chrzanowska-Lightowlers Z, et al
Biochem. J. 2017 06;474(13):2145-2158

Human Cytomegalovirus Infection Upregulates the Mitochondrial Transcription and Translation Machineries.
Karniely S, Weekes M, Antrobus R, Rorbach J, van Haute L, Umrania Y, et al
MBio 2016 Mar;7(2):e00029

Human mitochondrial ribosomes can switch their structural RNA composition.
Rorbach J, Gao F, Powell C, D'Souza A, Lightowlers R, Minczuk M, et al
Proc. Natl. Acad. Sci. U.S.A. 2016 10;113(43):12198-12201

Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs.
Gammage P, Gaude E, Van Haute L, Rebelo-Guiomar P, Jackson C, Rorbach J, et al
Nucleic Acids Res. 2016 09;44(16):7804-16

Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3.
Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce S, Powell C, et al
Nat Commun 2016 06;7():12039

Human Cytomegalovirus Infection Upregulates the Mitochondrial Transcription and Translation Machineries.
Karniely S, Weekes M, Antrobus R, Rorbach J, van Haute L, Umrania Y, et al
MBio 2016 Mar;7(2):e00029

TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies.
Powell C, Kopajtich R, D'Souza A, Rorbach J, Kremer L, Husain R, et al
Am. J. Hum. Genet. 2015 Aug;97(2):319-28

Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy.
Kopajtich R, Nicholls T, Rorbach J, Metodiev M, Freisinger P, Mandel H, et al
Am. J. Hum. Genet. 2014 Dec;95(6):708-20

MRM2 and MRM3 are involved in biogenesis of the large subunit of the mitochondrial ribosome.
Rorbach J, Boesch P, Gammage P, Nicholls T, Pearce S, Patel D, et al
Mol. Biol. Cell 2014 Sep;25(17):2542-55

Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations.
Gammage P, Rorbach J, Vincent A, Rebar E, Minczuk M
EMBO Mol Med 2014 04;6(4):458-66

Polyadenylation in bacteria and organelles.
Rorbach J, Bobrowicz A, Pearce S, Minczuk M
Methods Mol. Biol. 2014 ;1125():211-27

MPV17L2 is required for ribosome assembly in mitochondria.
Dalla Rosa I, Durigon R, Pearce S, Rorbach J, Hirst E, Vidoni S, et al
Nucleic Acids Res. 2014 Jul;42(13):8500-15

ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy.
Haack T, Kopajtich R, Freisinger P, Wieland T, Rorbach J, Nicholls T, et al
Am. J. Hum. Genet. 2013 Aug;93(2):211-23

Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease.
Kornblum C, Nicholls T, Haack T, Schöler S, Peeva V, Danhauser K, et al
Nat. Genet. 2013 Feb;45(2):214-9

The post-transcriptional life of mammalian mitochondrial RNA.
Rorbach J, Minczuk M
Biochem. J. 2012 Jun;444(3):357-73


Joanna Rorbach

Principal researcher
C2 Department of Medical Biochemistry and Biophysics

Visiting address

Biomedicum, 9D, floor 9
Solnavägen 9
171 65 Solna