Research Groups

Coenzyme A metabolism in health and disease

Ody Sibon’s research focuses on understanding the fundamental mechanisms underlying age-related neurodegeneration, with a particular emphasis on Coenzyme A (CoA) metabolism. Within the Sibon laboratory, research is directed at uncovering how disruptions in CoA biosynthesis contribute to rare neurological and cardiac diseases, including Pantothenate Kinase-Associated Neurodegeneration (PKAN). The lab applies a multidisciplinary approach, combining yeast, Drosophila melanogaster, mammalian cell systems, and mouse models to investigate how cells acquire, regulate, and utilize CoA.

A central aim of Ody Sibon’s work is to identify and characterize alternative pathways through which cells obtain CoA, challenging the traditional view that CoA is exclusively synthesized via vitamin B5-dependent pathways. The Sibon lab further explores how these mechanisms can be leveraged to develop novel therapeutic strategies. In addition, the group studies the interplay between host metabolism and the microbiome, with a particular focus on the exchange of CoA precursors between microbial communities and their host.

Overall, Ody Sibon’s research integrates fundamental and translational approaches, with the aim of advancing mechanistic insight and developing innovative treatments for CoA-related neurodegenerative and cardiac diseases .

  • People
  • Publications
  • Ody Sibon Visit
    Position

    Group leader of the Coenzyme A metabolism in health and disease

    Research fields

    Coenzyme A (CoA) metabolism, Neuroacanthocytosis, Pantothenate Kinase-Associated Neurodegeneration (PKAN), Neurodegeneration & Brain iron metabolism

    Postdoctoral Fellows
    Nicola Grzeschik
    Hein Schepers
    dakar-13
    Anna Yudenko
    PhD Students
    Jente Zeubring
    dakar-13
    Ting Xu
    Technicians
    Marianne van der Zwaag
    Ellie Eggens-Meijer
    • Hayflick SJ & Sibon OCM (2026) Neurodegeneration with brain iron accumulation – from gene discovery to therapeutic strategies Nature Reviews in Neurology (accepted 2nd Oct 2026)
    • Kiyuna LA, Odendaal C, Singh M, Gerding A, Langelaar-Makkinje M, van der Zwaag M, Drachman A, Cetkovská V, Kioen GLF, Martines AMF, Huijkman NCA, Schepers H, van de Sluis B, Reijngoud DJ, Sibon OCM, Harms AC, Hankemeier T, Bakker BM. (2026) Energetic stress in combination with impaired fatty acid oxidation induces sequestration of CoA and adaptation of CoA metabolism. FEBS Journal.
    • Grzeschik NA, Lambrechts RA, van der Zwaag M, Eggens-Meijer E, Sibon OCM, Gorter JA. (2025) Dysregulation of Glial Gap Junction Protein Innexin2 Mediates Seizures and Disrupted Sleep in a Drosophila Model for North Sea Progressive Myoclonus Epilepsy. Journal of Neuroscience Research.
    • Zhang F, Dorn T, Gnutti B, Anikster Y, Kuebler S, Ahrens-Nicklas R, Gosselin R, Rahman S, Durst R, Zanuttigh E, Güra MA, Poch CM, Meier AB, Laugwitz KL, Schüller HJ, Messias AC, Sibon OC, Finazzi D, Rippert A, Li D, Truxal K, Nandi D, Lampert BC, Yeo M, Gardham A, Nissan B, Horowitz Cederboim S, Moretti A, Iuso A. (2025) Pantethine ameliorates dilated cardiomyopathy features in PPCS deficiency disorder in patients and cell line models. Communications Medicine.
    • Wedman JJ, de Vries L, van Lingen B, van der Zwaag M, Gómez-Sánchez R, Hardenberg R, Huibers W, Permentier H, Strauss E, Chang M, Reggiori F, de Kroon AI, Sibon OCM, Schepers H. (2025) Opt1 imports CoA precursors as glutathione mixed disulfides. Journal of Biological Chemistry.
    • Böttcher J, Sibon OCM, El Aidy S. (2025) Coenzyme A metabolism: a key driver of gut microbiota dynamics and metabolic profiles. FEMS Microbiology Reviews.
    • Polet SS, de Koning TJ, Lambrechts RA, Tijssen MAJ, Sibon OCM, Gorter JA.(2024) Conventional and novel anti-seizure medications reveal a particular role for GABAA in a North Sea progressive myoclonus Epilepsy Drosophila model. Epilepsy Research.
    • Jouke Jan Wedman, Ody Sibon, E. Mastantuono, Aracangela Iuso. (2024) Impaired coenzyme A homeostasis in cardiac dysfunction and benefits of boosting coenzyme A production with vitamin B5 and its derivatives in the management of heart failure. Journal of Inherited Metabolic Disease
    • Hayflick SJ, Jeong SY, Sibon OCM. (2022) PKAN pathogenesis and treatment. Molecular Genetics and Metabolism.
    • Yu Y, van der Zwaag M, Wedman JJ, Permentier H, Plomp N, Jia X, Kanon B, Eggens-Meijer E, Buist G, Harmsen H, Kok J, Salles JF, Wertheim B, Hayflick SJ, Strauss E, Grzeschik NA, Schepers H, Sibon OCM. (2022) Coenzyme A precursors flow from mother to zygote and from microbiome to host. Molecular Cell.
    • Mostert KJ, Sharma N, van der Zwaag M, Staats R, Koekemoer L, Anand R, Sibon OCM, Strauss E. (2021) The Coenzyme A Level Modulator Hopantenate (HoPan) Inhibits Phosphopantotenoylcysteine Synthetase Activity. ACS Chemical Biology.
    • Yu Y, Moretti IF, Grzeschik NA, Sibon OCM, Schepers H. (2021) Coenzyme A levels influence protein acetylation, CoAlation and 4'-phosphopantetheinylation: Expanding the impact of a metabolic nexus molecule. Biochimica et Biophysica Acta Molecular Cell Research.
    • Faber AIE, van der Zwaag M, Schepers H, Eggens-Meijer E, Kanon B, IJsebaart C, Kuipers J, Giepmans BNG, Freire R, Grzeschik NA, Rabouille C, Sibon OCM. (2020) Vps13 is required for timely removal of nurse cell corpses. Development.
    • Lambrechts RA, Polet SS, Hernandez-Pichardo A, van Ninhuys L, Gorter JA, Grzeschik NA, de Koning-Tijssen MAJ, de Koning TJ & Sibon OCM. (2019) North Sea progressive myoclonus epilepsy is exacerbated by heat, a phenotype primarily associated with affected glia. Neuroscience.
    • Roald Lambrechts, Yu Yi, Hein Schepers, Marianne van der Zwaag, Kaija Autio, Marina A. Tijssen, Susan Hayflick, Nicola Grzeschik, Ody Sibon. (2019) CoA-dependent activation of mitochondrial acyl carrier protein links four neurodegenerative diseases. EMBO Molecular Medicine.
    • Suh Young Jeong, Penelope Hogarth, Andrew Placzek, Allison M Gregory, Rachel Fox, Dolly Zhen, Jeffrey Hamada, Marianne van der Zwaag, Roald Lambrechts, Haihong Jin, Aaron Nilsen, Jared Cobb, Thao Pham, Nora Gray, Martina Ralle, Megan Duffy, Leila Schwanemann, Puneet Rai, Alison Freed, Katrina Wakeman, Randy Woltjer, Ody C.M. Sibon, & Susan J Hayflick. (2019). 4’-Phosphopantetheine corrects CoA, iron and dopamine metabolic defects in mammalian models of PKAN. EMBO Molecular Medicine.
    • Matteo Bason, Melanie Meister-Broekema, Niels Alberts, Pascale Dijkers, Steven Bergink, Ody C.M. Sibon and Harm H. Kampinga. (2019). Astrocytic expression of the chaperone DNAJB6 results in non-cell autonomous protection in Huntington’s disease. Neurobiology of Disease.
    • Yeshaw WM, van der Zwaag M, Pinto F, Lahaye LL, Faber AI, Gómez-Sánchez R, Dolga AM, Poland C, Monaco AP, van IJzendoorn S, Grzeschik NA, Velayos-Baeza A, Sibon OCM. (2019) Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility. eLife
    • Yixian Li, Sibon Ody C.M, Pascale Dijkers. (2018) Inhibition of NF-κB in astrocytes is sufficient to delay neurodegeneration induced by proteotoxicity in neurons. Journal of Neuroinflammation.
    • Arcangela Iuso, Marit Wiersma, Hans-Joachim Schüller, Ben Pode-Shakked, Dina Marek-Yagel, Mathias Grigat, Thomas Schwarzmayr, Riccardo Berutti, Bader Alhaddad, Bart Kanon, Nicola A. Grzeschik, Jürgen G. Okun, Zeev Perles, Yishay Salem, Ortal Barel, Amir Vardi, Marina Rubinshtein, Tal Tirosh, Gal Dubnov-Raz, Ana C Messias, Caterina Terrile, Iris Barshack, Alex Volkov, Camilla Avivi, Eran Eyal, Elisa Mastantuono, Muhamad Kumbar, Shachar Abudi, Matthias Braunisch,Tim M Strom, Thomas Meitinger, Georg F Hoffmann, Holger Prokisch, Tobias B Haack, Bianca JJM Brundel, Dorothea Haas*, Ody CM Sibon*,Yair Anikster* (2018) Mutations in phosphopantothenoylcysteine synthetase (PPCS) cause dilated cardiomyopathy. *shared last author American Journal of Human Genetics.
    • Andrea Soto-Padilla, Rick Ruijsink, Ody C.M. Sibon, Hedderik van Rijn, Jean-Christophe Billeter. (2018) Thermosensory perception regulates speed of movement in response to temperature changes in Drosophila melanogaster. This paper was selected as a 2018 highlight. Journal of Experimental Biology.
    • Marit Wiersma, Roelien A.M. Meijerin, XiaoYan Qi, Deli Zhang, Tao Liu, Femke Hoogstra-Berends, Ody C.M. Sibon, Robert H. Henning, Stanley Nattel, Bianca J.J.M. (2018) Brundel Endoplasmic reticulum stress is associated with autophagy and cardiomyocyte remodeling in experimental and human Atrial Fibrillation. Journal of the American Heart Association.
    • Ivano Di Meo, Cristina Colombelli, Balaji Srinivasan, Marianne de Villiers, Jeffrey Hamada, Suh Y. Jeong, Rachel Fox, Randall L. Woltjer, Pieter G. Tepper, Liza L. Lahaye, Emanuela Rizzetto, Clara H. Harrs, Theo de Boer, Marianne van der Zwaag, Branko Jenko, Alen Čusak, Jerca Pahor, Gregor Kosec, Nicola A. Grzeschik, Susan J. Hayflick, Valeria Tiranti, Ody C.M. Sibon (2017). Acetyl-4’-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency. Scientific Reports.
    • Pappas SS, Bonifacino J, Danek A, Dauer WT, De M, De Franceschi L, DiPaolo G, Fuller R, Haucke V, Hermann A, Kornmann B, Landwehrmeyer B, Levin J, Neiman AM, Rudnicki DD, Sibon O, Velayos-Baeza A, Vonk JJ, Walker RH, Weisman LS, Albin RL. (2017) Eighth International Chorea-Acanthocytosis Symposium: Summary of Workshop Discussion and Action Points. Tremor Other Hyperkinet Movements .
    • Jan J. Vonk, Wondwossen M. Yeshaw, Francesco Pinto, Liza L. Lahaye, Anita I.E. Faber, Bart Kanon, Marianne van der Zwaag, Antonio Velayos-Baeza, Raymundo Freire, Sven C. van Ijzendoorn, Nicola A. Grzeschik, Ody C.M. Sibon (2017) Drosophila Vps13 is required for protein homeostasis in the brain PLoS One
    • Ody C.M. Sibon & Erick Strauss (2016) Coenzyme A: to make it or uptake it? Nature reviews.
    • Michel J. Vos, Serena Carra, bart Kanon, Floris Bosveld, Karin Klauke, Ody C.M. Sibon* and Harrie H. (2016) Kampinga* Specific protein homeostatic functions of small heat shock proteins increase lifespan. Aging Cell *shared last author
    • Roland F. Hoffmann, Yuri M. Moshkin, Stijn Mouton, Nicola A. Grzeschik, Ruby D. Kalicharan, Jeroen Kuipers, Anouk H. G. Wolters, Kazuki Nishida, Aleksander V. Romashchenko, Jan Postberg, Hans Lipps, Eugene Berezikov, Ody C. M. Sibon, Ben N. G. Giepmans and Peter M. Lansdorp (2016) Guanine quadruplex structures localize to heterochromatin Nucleic Acid Research
    • Pauline M. Snijder, Madina Baratashvili, Nicola A. Grzeschik, Henri G.D. Leuvenink, Lucas Kuijpers, Sippie Huitema, Onno Schaap, Ben N.G. Giepmans, Jeroen Kuipers, Jan Lj. Miljkovic, Aleksandra Mitrovic, Eelke M. Bos, Csaba Szabó, Harm H. Kampinga, Pascale F. Dijkers, Wilfred F.A. den Dunnen, Milos R. Filipovic, Harry van Goor, Ody C. M. Sibon (2015) Overexpression of cystathionine γ-lyase suppresses detrimental effects of spinocerebellar ataxia type 3 Molecular Medicine
    • B. Srinivasan, M. Baratashvili, M. Van der Zwaag, B. Kanon, C. Colombelli, R.A. Lambrechts, O. Schaap, E.A.A. Nollen, A. Podgoršek, G. Kosec, H. Petković, S. Hayflick, V. Tiranti, D.J. Reijngoud, N.A. Grzeschik, Ody C.M. Sibon (2015) Extracellular 4’-Phosphopantetheine is a source for intracellular Coenzyme A synthesis. Nature Chemical Biology
    • Theodoulou FL, Sibon OCM, Jackowski S, Gout I (2014) Coenzyme A and its derivatives; renaissance of a textbook classic Biochemical Society Transactions
    • B. Srinivasan, Ody C.M. Sibon. (2014) Coenzyme A, more than “just” a metabolic cofactor. Biochemical Society Transactions.
    • Arcangela Iuso, Ody CM Sibon, Matteo Gorza, Katharina Heim, Cristina Organisti, Thomas Meitinger, Holger Prokisch.(2014) Impairment of Drosophila Orthologs of the Human Orphan Protein C19orf12 Induces Bang Sensitivity and Neurodegeneration. PLoS One
    • Brunetti D, Dusi S, Giordano C, Lamperti C, Morbin M, Marchet S, Fagiolari G, Sibon OCM, Moggio M, d’Amati G, and Tiranti V. (2014) Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a Pank2 knock-out mouse model Brain
    • Zhang D, Meijering RAM, Hoogstra-Berends F, Cubukcuoglu Deniz G, Durdu S, Akar R, Sibon OCM, Henning RH, Brundel BJJM. (2014) HDAC6 causes derailment of α-tubulin proteostasis and contractile dysfunction in experimental and human Atrial Fibrillation. Circulation
    • Den Hoed M. et al , Sibon OCM, Milan DJ, Schnieder H, Samani NJ, Loos RJF. (2013) Identification of Heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nature Genetics
    • Siudeja K, Grzeschik NA, Rana A, de Jong J, Sibon OCM. (2012) Cofilin/Twinstar phosphorylation levels increase in response to impaired Coenzyme A metabolism. PLoS One
    • Prohaska R, Sibon OCM, Rudnicki DD, Danek A, Hayflick SJ, Verhaag EM, Vonk JJ, Margolis RL, Walker RH. (2012) Brain, blood, and iron: Perspectives on the roles of erythrocytes and iron in neurodegeneration. Neurobiology of Disease
    • Katarzyna Siudeja K, Xu L, Srinivasan B, Rana A, Jong JJ,Jackowski S, Hayflick S and Sibon OCM (2011) Impaired Coenzyme A metabolism affects histone and tubulin acetylation in a Drosophila and human cell model of the neurodegenerative disorder PKAN. EMBO Molecular Medicine
    • Zhang D, Ke L, Mackovicova K, Van Der Want JLJ, Sibon OCM, Robert M. Tanguay RM, Morrow G, Henning RH, Kampinga HH, Brundel BJJM (2011) Effects of different small HSPB members on contractile dysfunction and structural changes in a Drosophila melanogaster model for Atrial Fibrillation Journal of Molecular and Cell Cardiology
    • Seinen E, Burgerhof JGM, Jansen RC, Sibon OCM. (2011) RNAi-induced off-target effects in Drosophila melanogaster: frequencies and solutions. Briefings in Functional Genomics
    • Vos M, Zijlstra MP, Carra S, Sibon OCM, Kampinga HH. (2011) Small heat shock proteins, protein degradation and protein aggregation diaseases. Autophagy
    • Seinen E, Burgerhof JGM, Jansen RC, Sibon OCM. (2010) RNAi experiments in D. melanogaster: solutions to the overlooked problem of off-targets shared by independent dsRNAs. PloS One
    • Carra S, Boncoraglio A, Kanon B, Brunsting JF, Minoia M, Rana A, Vos MJ, Seidel K, Sibon OCM*, Kampinga HH*.(2010) Identification of the Drosophila ortholog of HSPB8: on the role of HSPB8 in protein folding diseases Journal of Biological Chemistry *Shared last author
    • Vos. MJ, Zijlstra MP, Kanon B, van Waarde MAWH, Brunt ER, Oosterveldt- Hut HMJ, Carra S, Sibon OCM, Kampinga HH.(2010) A comparative screen of the human HSPB family of molecular chaperones reveals HSBP7 as a superior suppressor of aggregation of polyglutamine containing proteins. Human Molecular Genetics
    • Rana A, Seinen E, Siudeja K, Muntendam R, Srinivasan B, van der Want J, Hayflick S, Reijngoud D, Kayser O, Sibon OCM. (2010) Pantethine rescues a Drosophila model for Pantothenate Kinase-Associated Neurodegeneration. The Proceedings of the National Academy of Sciences U S A.
    • Tan, Lu Ping T, Seinen E, Duns G, de Jong D, Sibon OCM, Poppema S, Kroesen B-J, Kok K, van den Berg A.(2009) A high throughput experimental approach to identify miRNA targets in human cells. Nucleic Acids Research
    • Yi X, de Vries H, Siudeja K, Lemstra W, Brunsting J, Dijk F, Shang Y, Eggen BJL, Kampinga HH and Sibon OCM. (2009) Stwl modifies chromatin compaction and is required to maintain DNA integrity in the presence of perturbed DNA replication. Molecular Biology of the Cell
    • Bosveld F, Rana A, Lemstra W, Kampinga HH, Sibon OCM. (2008) Drosophila phosphopantothenoylcysteine synthetase is required for tissue morphogenesis during oogenesis. BMC Research Notes
    • Yi X, Lemstra W, Vos MJ, Shang Y, Kampinga HH, Su TT, Sibon OCM. (2008) A long term FCM assay to analyze the role of specific genes of Drosophila melanogaster S2 cells in surviving genotoxic stress. Cytometry Part A
    • Bosveld F, Rana A, van der Wouden P, Lemstra W, Ritsema M, Kampinga HH, Sibon OCM. (2008) De novo CoA biosynthesis is required to maintain DNA integrity during development of the Drosophila nervous system. Human Molecular Genetics
    • Bosveld F, van Hoek S, Sibon OCM. (2008) Establishment of cell fate during early Drosophila embryogenesis required transcriptional Mediator subunit dMED31. Development Biology
    • Rujano MA, Bosveld B, Salomons FA, Dijk F, van Waarde MAWH, van der Want JJL, de Vos RAI, Brunt ER, Sibon OCM, Kampinga HH.(2006) Polarized asymmetric inheritance of accumulated protein damage in higher eukaryotes. PloS Biology
    • Jaklevic B, Uyetake L, Lemstra W, Chang J, Leary W, Edwards A, Vidwans S, Sibon OCM, Su TT. (2006) Contribution of growth and cell cycle checkpoints to radiation survival in Drosophila. Genetics
    • Hut HM, Rembacz KP, van Waarde MA, Lemstra W, van Cappellen WA, Kampinga HH, Sibon OCM. (2005) Dysfunctional BRCA1 is only indirectly linked to multiple centrosomes. Oncogene.
    • Hut HM, Kampinga HH, Sibon OCM. (2005) Hsp70 protects mitotic cells against heat-induced centrosome damage and division abnormalities. Molecular Biology of the Cell.
    • de Vries HI, Uyetake L, Lemstra W, Brunsting JF, Su TT, Kampinga HH, Sibon OCM. (2005) Grp/DChk1 is required for G2-M checkpoint activation in Drosophila S2 cells, whereas Dmnk/DChk2 is dispensable. Journal of Cell Science
    • Sibon OCM. (2003) Centrosomes as DNA damage regulators. Nature Genetics.
    • Hut HMJ, Lemstra W, Blaauw EH, van Cappellen GWA, Kampinga HH, Sibon OCM. (2003) Centrosomes split in the presence of impaired DNA integrity during mitosis. Molecular Biology of the Cell.
    • Khodjakov A, Rieder CL, Sluder G, Cassels G, Sibon OCM, Wang CL. (2002) De novo formation of centrosomes in vertebrate cells arrested during S phase. Journal of Cell Biology.
    • Nollen EA, Salomons FA, Brunsting JF, Want JJ, Sibon OCM, Kampinga HH. (2001) Dynamic changes in the localization of thermally unfolded nuclear proteins associated with chaperone-dependent protection. The Proceedings of the National Academy Sciences U S A.
    • Sibon OCM, Kelkar A, Lemstra W, Theurkauf WE. (2000) DNA-replication/DNA-damage-dependent centrosome inactivation in Drosophila embryos. Nature Cell Biology.
    • Sibon OCM, Laurencon A, Hawley R, Theurkauf WE. (1999) The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition. Current Biology.
    • Sibon OCM, Stevenson VA, Theurkauf WE. (1997) DNA-replication checkpoint control at the Drosophila midblastula transition. Nature.
    • Luderus ME, van Steensel B, Chong L, Sibon OCM, Cremers FF, de Lange T.(1996) Structure, subnuclear distribution, and nuclear matrix association of the mammalian telomeric complex. Journal of Cell Biology.
    • Sibon OCM, Wansink DG, Boonstra J, Humbel BM, Verkleij AJ, Cremers FF. (1996) EGF-receptor RNA metabolism in the nucleus of A431 cells. European Journal of Cell Biology.
    • Wansink DG, Sibon OCM, Cremers FF, van Driel R, de Jong L.(1996) Ultrastructural localization of active genes in nuclei of A431 cells. Journal of Cellular Biochemisty
    • Humbel BM, Sibon OCM, Stierhof YD, Schwarz H. (1995) Ultra-small gold particles and silver enhancement as a detection system in immunolabeling and in situ hybridization experiments. Journal of Histochemistry & Cytochemistry
    • Sibon OCM, Cremers FF, Humbel BM, Boonstra J, Verkleij AJ.(1995) Localization of nuclear RNA by pre- and post-embedding in situ hybridization using different gold probes. Histochemical Journal.
    • Sibon OCM, Humbel BM, De Graaf A, Verkleij AJ, Cremers FF.(1994) Ultrastructural localization of epidermal growth factor (EGF)-receptor transcripts in the cell nucleus using pre-embedding in situ hybridization in combination with ultra-small gold probes and silver enhancement. Histochemistry.
    • Sibon OCM, Cremers FF, Boonstra J, Humbel BM, Verkleij AJ.(1993) Localisation of EGF-receptor mRNA in the nucleus of A431 cells by light microscopy. Cell Biology International.
Share this:
Your browser is out-of-date!

Update your browser to view this website correctly. Update my browser now

×