Phospholipids are imported into mitochondria by VDAC, a dimeric beta barrel scramblase
Jahn H, Bartoš L, Dearden GI, Dittman JS, Holthuis JCM, Vácha R, Menon AK. (2023) Nat Commun. 14(1):8115. [pdf]

Toxoplasma ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness
Koutsogiannis Z, Mina JG, Albus CA, Kol MA, Holthuis JCM, Pohl E, Denny PW. (2023) FASEB J 37, e23229 – [pdf]

Systematic analysis of the sphingomyelin synthase family in C. elegans
Guzman GG, Farley S, Kyle JE, Bramer LM, Hoeltzl S, van den Dikkenberg J, Holthuis JCM*, Tafesse FG*. (2023) bioRxiv 2023 Jul 25:2023.07.25.550547 [pdf]

Membrane damage and repair: a thin line between life and death
Barisch C, Holthuis J, Cosentino C (2023) Biol. Chem. 404, 467-490 [pdf]


Biofunctional nanodot arrays in living cells uncover synergistic co-condensation of Wnt signalodroplets
Philippi M, Richter CP, Kappen M, Watrinet I, Miao Y, Runge M, Jorde L, Korneev S, Holtmannspötter M, Kurre R, Holthuis JCM, Garcia KC, Plückthun A, Steinhart M, Piehler J, You C (2022) bioRxev [pdf]

Pathogenic variants of sphingomyelin synthase SMS2 disrupt lipid landscapes in the secretory pathway
Sokoya T, Parolek J, Foged MM, Danylchuk DI, Bozan M, Sarkar B, Hilderink A, Philippi M, Botto LD, Terhal PA, Mäkitie O, Piehler J, Kim Y, Burd CG, Klymchenko AS, Maeda K, Holthuis JCM. (2022) Elife. 11:e79278. [pdf]

An alliance between lipid transfer proteins and scramblases for membrane expansion
Holthuis JCM, Jahn H, Menon AK, Mizushima N. (2022) Fac Rev. 11:22. [pdf]

Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair. Niekamp P, Scharte F, Sokoya T, Vittadello L, Kim Y, Deng Y, Südhoff E, Hilderink A, Imlau M, Clarke CJ, Hensel M, Burd CG, Holthuis JCM (2022) Nature Communications 13:1875, doi: 10.1038/s41467-022-29481-4 [pdf]


Short photoswitchable ceramides enable optical control of apoptosis. Morstein J, Kol M, Novak AJE, Feng S, Khayyo S, Hinnah K, Li-Purcell N, Pan G, Williams BM, Riezman H, Atilla-Gokcumen GE, Holthuis JCM, Trauner D (2021) ACS Chem Biol. 2021, 16(3), 452–456 doi: 10.1021/acschembio.0c00823 [pdf]

Sphingomyelin biosynthesis is essential for phagocytic signaling during Mycobacterium tuberculosis cell entry. Niekamp P, Guzman G, Leier HC, Rashidfarrokhi A, Richina V, Pott F, Barisch C, Holthuis JCM*, Tafesse FG* (2021) mBio 12, e03141-20 [pdf]


A switchable ceramide transfer protein for dissecting the mechanism of ceramide-induced mitochondrial apoptosis. Jain A, Dadsena S, Holthuis JC (2020) FEBS Letters 594, 3739-3750 [pdf]


Unraveling the molecular principles by which ceramides commit cells to death. Dadsena S, Hassan D, Holthuis JC (2019) Cell Stress 3, 280-283 [pdf]

Ceramides bind VDAC2 to trigger mitochondrial apoptosis. Dadsena S, Bockelmann S, Mina JG, Hassan D, Korneev S, Razzera G, Jahn H, Niekamp P, Müller D, Schneider M, Tafesse FG, Marrink SJ, Melo MN, Holthuis JC (2019) Nature Communications 10,1832 [pdf]

Osteoporosis and skeletal dysplasia caused by pathogenic variants in SGMS2. Pekkinen M, Terhal PA, Botto LD, Henning P, Mäkitie RE, Roschger P, Jain A, Kol M, Kjellberg MA, Paschalis EP, van Gassen K, Murray M, Bayrak-Toydemir P, Magnusson MK, Jans J, Kausar M, Carey JC, Somerharju P, Lerner UH, Vesa OM;. Klaushofer K, Holthuis JC, Mäkitie O (2019) JCI Insight, Doi: 10.1172/jci.insight.126180 [pdf]

Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides. Kol M, Williams B, Toombs-Ruane H, Franquelim HG, Korneev S, Schroeer C, Schwille P, Trauner D*, Holthuis JC*, Frank JA* (2019) eLife Feb 5;8. pii: e43230. doi: 10.7554/eLife.43230 [pdf]


Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants. Kunduri G, Turner-Evans D, Konya Y, Nagashima K, Lockett S, Holthuis JC, Bamba T, Acharya U, Acharya JK. (2018) PNAS, Doi: 10.1073/pnas.1808463115 [pdf]

A search for ceramide binding proteins using bifunctional lipid analogues yields CERT-related protein StarD7. Bockelmann S, Mina JGM, Korneev S, Hassan DG, Müller D, Hilderink A, Vlieg HC, Raijmakers R, Heck AJR, Haberkant P, Holthuis JC. (2018) J. Lipid Res. 59, 515-530 [pdf]


Ceramide phosphoethanolamine synthase SMSr is a target of caspase-6 during apoptotic cell death. Cabukusta B, Nettebrock NT, Kol M, Hilderink A, Tafesse FG, Holthuis JC. (2017) Biosci. Rep. 37, 4. pii: BSR20170867. [pdf]

Membrane contacts, ancient and central hubs of cellular lipid logistics. Jain A, Holthuis JC. (2017) Biochim. Biophys. Acta 1864, 1450-1458 [pdf]

ER residency of the ceramide phosphoethanolamine synthase SMSr relies on homotypic oligomerization mediated by its SAM domain. Cabukusta B, Kol M, Kneller L, Hilderink A, Bickert A, Mina J, Korneev S, Holthuis JC. (2017) Sci. Rep. 7, 41290 [pdf]

Diverting CERT-mediated ceramide transport to mitochondria triggers Bax-dependent apoptosis. Jain A, Beutel O, Ebell K, Korneev S, Holthuis JC. (2017) J. Cell Sci. 130, 360-371 [pdf]


Monitoring changes in the oligomeric state of a candidate ER ceramide sensor by single-molecule photobleaching. Cabukusta B, Köhlen JA, Richter CP, You C, Holthuis JC. (2016) J. Biol. Chem. 291, 24735-24746 [pdf]

Switching head group selectivity in mammalian sphingolipid biosynthesis by active-site engineering of sphingomyelin synthases. Kol M, Panatala R, Nordmann M, Swart L, van Suijlekom L, Cabukusta B, Hilderink A, Grabietz T, Mina JG, Somerharju P, Korneev S, Tafesse FG, Holthuis JC. (2016) J. Lipid Res. 57, 1273-1285 [pdf]


Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice. Bickert A, Ginkel C, Kol M, vom Dorp K, Jastrow H, Degen J, Jacobs RL, Vance DE, Winterhager E, Jiang XC, Dörmann P, Somerharju P, Holthuis JC*, Willecke K*. (2015) J. Lipid Res. 56, 821-835 [pdf]

Inner workings and biological impact of phospholipid flippases. Panatala R, Hennrich H, Holthuis JC. (2015) J. Cell Sci. 128, 2021-2032 [pdf]


Lipid landscapes and pipelines in membrane homeostasis. Holthuis JC and Menon AK (2014) Nature 510, 48-57 [pdf]

Sphingomyelin synthase-related protein SMSr is a suppressor of ceramide-induced mitochondrial apoptosis. Tafesse FG, Vacaru AM, Bosma EF, Hermansson M, Jain A, Hilderink A, Somerharju P, Holthuis JC (2014) J. Cell Sci. 127, 445-454 [pdf]

Fat and fabulous: bifunctional lipids in the spotlight. Haberkant P and Holthuis JC (2014) Biochim. Biophys. Acta, 1841, 1022-1030 [pdf]


In vivo profiling and visualization of cellular protein-lipid interactions using bifunctional fatty acids. Haberkant P, Raijmakers R, Wildwater M, Sachsenheimer T, Brügger B, Maeda K, Houweling M, Gavin AC, Schultz C, van Meer G, Heck AJ, Holthuis JC (2013) Angew. Chem. Int. Ed. Engl. 52, 4033-4038 [pdf]

Ceramide phosphoethanolamine biosynthesis in Drosophila is mediated by a unique ethanolamine phosphotransferase in the Golgi lumen. Vacaru AM, van den Dikkenberg J, Ternes P, Holthuis JC (2013) J. Biol. Chem. 288, 11520-11530 [pdf]

Cellular microcompartments constitute general suborganellar functional units in cells. Holthuis JC, Ungermann C. (2013) Biol. Chem. 394, 151-161 [pdf]


Mapping functional interactions in a heteromeric phospholipid pump. Puts CF, Panatala Narendranath R, Tsavera A, Williamson P, Holthuis JC (2012) J. Biol. Chem. 287, 30529-30540 [pdf]

Phosphatidylserine stimulation of Drs2p-Cdc50p lipid translocase dephosphorylation is controlled by phosphatidyl-4-phosphate. Jacqout A, Montigny C, Hennrich H, Barry R, le Maire M, Jaxel C, Holthuis JC, Champeil P, Lenoir G (2012) J. Biol. Chem. 287, 13249-13261 [pdf]

Flip or flop: mechanism and pathophysiology of P4-ATPase-catalyzed lipid transport. Verhulst PM, Holthuis JC*, Pomorski TG* (2012) In Transmembrane dynamics of lipids, Devaux PF and Herrmann A, Eds. John Wiley & Sons, Hoboken, NJ, USA [pdf]


Pumping lipids with P4-ATPases. Lopez-Marques R, Holthuis JC*, Pomorski TG* (2011) Biol. Chem. 392, 67-76 [pdf]


In vivo cross-linking of a P4-ATPase protein interaction network reveals a link between aminophospholipid transport and phosphoinositide metabolism. Puts CF, Lenoir G, Krijgsveld J, Williamson P, Holthuis JC (2010) J. Proteome Res. 9, 833-842 [pdf]

Cdc50 proteins are critical components of the human ATP8 subfamily of putative phospholipidtransporters. Bryde S, Hennrich H, Verhulst PM, Devaux PF, Lenoir G, Holthuis JC (2010) J. Biol. Chem. 287, 30529-30540 [pdf]

A brake on lipid synthesis. Tafesse FG, Holthuis JC (2010) Nature 463, 1028-1029 [pdf]

A flippase-independent function of ATP8B1, the protein affected in familial intrahepatic cholestasis type 1, is required for apical protein expression and microvillus formation in polarized epithelial cells. Verhulst PM, van der Velden LM, Oorschot V, van Faassen EE, Klumperman J, Houwen RHJ, Pomorski TG, Holthuis JC*, Klomp LWJ* (2010) Hepatology 51, 2049-2060 [pdf]

Folding defects in ATP8B1 associated with hereditary cholestasis are ameliorated by 4-phenylbutyrate. Van der Velden LM, Stapelbroek JS, Krieger E, van den Berghe, PVE, Berger R, Verhulst PM, Holthuis JC, Houwen RHJ, Klomp LW, van de Graaf SFJ (2010) Hepatology 51, 286-296 [pdf]

Tales and mysteries of the enigmatic sphingomyelin synthase family. Holthuis JC, Luberto C. (2010) Adv. Exp. Med. Biol. 688, 72-85 [pdf]


Membrane contact sites between apicoplast and ER in Toxoplasma gondii revealed by Electron Tomography. Tomova C, Humbel BM, Geerts WJ, Entzeroth R, Holthuis JC, Verkleij AJ (2009) Traffic 10, 1471-1480 [pdf]

Sphingomyelin synthase SMS2 displays dual activity as ceramide phosphoethanolamine synthase. Ternes P, Brouwers JF, van den Dikkenberg J, Holthuis JC (2009) J. Lipid Res. 50, 2270-2277 [pdf]

Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER. Vacaru AM, Tafesse FG, Ternes P, Kondylis V, Hermansson M, Brouwers JF, Somerharju P, Rabouille C, Holthuis JC (2009) J. Cell Biol. 185, 1013-1027 [pdf]

Cdc50p plays a vital role in the ATPase reaction cycle of the putative aminophospholipid transporter Drs2p. Lenoir G, Williamson P, Puts CF, Holthuis JC (2009) J. Biol. Chem. 284, 17956-17967 [pdf]

Mechanism and significance of P4 ATPase-catalysed lipid transport: lessons from a Na+/K+-pump. Puts CF, Holthuis JC (2009) BBA Mol. Cell. Biol. Lipids 1791, 603-611 [pdf]


On the origin of lipid asymmetry: the flip side of ion transport. Lenoir G, Williamson P, Holthuis JC (2007) Curr. Op. Chem. Biol. 11, 654-661 [pdf]

Both sphingomyelin synthase SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells. Tafesse FG, Huitema K, Hermansson M, van der Poel S, van den Dikkenberg J, Uphoff A, Somerharju P, Holthuis JC (2007) J. Biol. Chem. 282, 17537-17547 [pdf]

The multigenic sphingomyelin synthase family. Tafesse FG, Ternes P, Holthuis JC (2006) J. Biol. Chem. 281, 29421-29425 [pdf]


Loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and asymmetry in yeast post-Golgi secretory vesicles. Alder-Baerens N, Lisman Q, Luong L, Pomorski T, Holthuis JC (2006) Mol. Biol. Cell. 17, 1632-1642 [pdf]

The CLN9 protein, a regulator of dihydroceramide synthase. Schulz A, Mousallem T, Venkataramani M, Persaud-Sawin DA, Zucker A, Luberto C, Bielawska A, Bielawski J, Holthuis JC, Jazwinski SM, Kozhaya L, Dbaibo GS and Boustany RM (2006) J. Biol. Chem. 281, 2784-2794 [pdf]


Lipid traffic: floppy drives and a superhighway. Holthuis JC, Levine T (2005) Nat. Rev. Mol. Cell Biol. 6, 209-220 [pdf]


Identification of a family of animal sphingomyelin synthases. Huitema K, Van Den Dikkenberg J, Brouwers JF, Holthuis JC (2004) EMBO J. 23, 33-44 [pdf]

The elusive flippases. Lenoir G, Holthuis JC (2004) Curr. Biol. 14, R912-913 [pdf]

HOR7, a multicopy suppressor of the Ca2+-sensitive growth defect in sphingolipid mannosyltransferase-deficient yeast. Lisman Q, Urli-Stam D, Holthuis JCM (2004) J. Biol. Chem. 279, 36390-36396 [pdf]

Tracking down lipid flippases and their biological functions. Pomorski T, Holthuis JC, Herrmann A, Van Meer G (2004) J. Cell Sci. 117, 805-13 [pdf]

Protein sorting in the late Golgi of Saccharomyces cerevisiae does not require mannosylated sphingolipids. Lisman Q, Pomorski T, Vogelzangs C, Urli-Stam D, de Cocq van Delwijnen W, Holthuis JC (2004) J. Biol. Chem. 279, 1020-1029 [pdf]


Drs2p-related P-type ATPases Dnf1p and Dnf2p are required for phospholipid translocation across the yeast plasma membrane and serve a role in endocytosis. Pomorski T, Lombardi R, Riezman H, Devaux PF, van Meer G, Holthuis JC (2003) Mol. Biol. Cell 14, 1240-1254 [pdf]

Sensing membrane curvature. Holthuis JC, Burger KN (2003) Dev. Cell 5, 821-822 [pdf]

Lipid microdomains, lipid translocation and the organization of intracellular membrane transport. Holthuis JC, van Meer G, Huitema K (2003) Mol. Membr. Biol. 20, 231-241 [pdf]


The organising potential of sphingolipids in intracellular membrane transport. Holthuis JC, Pomorski T, Raggers RJ, Sprong H, van Meer G (2001) Physiol. Rev. 81, 1689-1723 [pdf]


Lipid Traffic: The ABC of transbilayer lipid movement. Raggers RJ, Pomorski T, Holthuis JC, Kälin N, van Meer G (2000) Traffic 1, 226-234 [pdf]

Inhibition of the vacuolar H+-ATPase perturbs the transport, sorting, processing and release of regulated secretory proteins. Schoonderwoert VTG, Holthuis JC, Tanaka S, Tooze SA, Martens GJM (2000) Eur. J. Biochem. 267, 5646-5654 [pdf]

Sphingolipid transport in eukaryotic cells. Van Meer G, Holthuis JC (2000) BBA Mol. Cell. Biol. Lipids 1486, 145-170 [pdf]


Biosynthesis of the vacuolar H+-ATPase accessory subunit Ac45 in Xenopus pituitary. Holthuis JC, Jansen EJ, Schoonderwoert VT, Burbach JP, Martens GJM (1999) Eur. J. Biochem. 262, 484-491 [pdf]

The syntaxin Tlg1p mediates trafficking of chitin synthase III to polarized growth sites in yeast. Holthuis JC, Nichols BJ, Pelham HRB (1998) Mol. Biol. Cell 9, 3383-3397 [pdf]

Two syntaxin homologs in the TGN/endosomal system of yeast. Holthuis JC, Nichols BJ, Dhruvakumar S, Pelham HRB (1998) EMBO J. 17, 113-126 [pdf]

The Sec1p homologue Vps45p binds to the syntaxin Tlg2p. Nichols BJ, Holthuis JC, Pelham HRB (1998) Eur. J. Cell Biol. 77, 263-268 [pdf]

Intracellular trafficking of the vacuolar H+-ATPase accessory subunit Ac45. Jansen EJR, Holthuis JC, McGrouther C, Burbach JP, Martens GJM (1998) J. Cell Sci. 111, 2999-3006 [pdf]

Secretogranin III is a sulfated protein undergoing proteolytic processing in the regulated secretory pathway. Holthuis JC, Jansen EJR, and Martens GJM (1996) J. Biol. Chem. 271, 17755-17760 [pdf]

The neuroendocrine proteins secretogranin II and III are regionally conserved and coordinately expressed with proopiomelanocortin in Xenopus intermediate pituitary. Holthuis JC, Martens GJM (1996) J. Neurochem. 66, 2248-2256 [pdf]


Molecular probing of the secretory pathway in peptide hormone-producing cells. Holthuis JC, Jansen EJR, van Riel MHCM, Martens GJM (1995) J. Cell Sci. 108, 3295-3305 [pdf]

Translocon-associated protein TRAPδ and a novel TRAP-like protein are coordinately expres­sed with proopio-melanocortin in Xenopus intermediate pituitary. Holthuis JC, van Riel MHCM, Martens GJM (1995) Biochem. J. 312, 205-213 [pdf]

A vertebrate homolog of the actin-bundling protein fascin. Holthuis JC, Schoonderwoert VTG, Martens GJM (1994) BBA Gene Struct. Expr. 1219, 184-188 [pdf]

The activation of blood coagulation factor X on the surface of endothelial cells: a comparison with various vascular cells, platelets and monocytes. Brinkman HJM, Mertens K, Holthuis JC, Zwart-Huinink LA, Grijm K, van Mourik JA (1994) Brit. J. Haematol. 87, 332-342 [pdf]

Prevention of side effects by hemoglobin solutions: the selection of optimal testmodels, especially concerning thrombogenity. Bakker JC, Bleeker WK, Den Boer PJ, Biessels PTM, Achterberg J, Rigter G, Holthuis JC, Mertens K (1994) Artif. Cells Blood Substit. Immobil. Biotech. 22, 577-585 [pdf]

Coordination of protein-DNA interactions in the promoters of human H4, H3, and H1 histone genes during the cell cycle, tumorigenesis, and development. Van Wijnen AJ, Owen TA, Holthuis JC, Lian JB, Stein JL, Stein GS (1991) J. Cell. Physiol. 148, 174-189 [pdf]

Tumor cells exhibit deregulation of the cell cycle histone gene promoter factor HiNF-D. Holthuis JC, Owen TA, van Wijnen AJ, Wright KL, Ramsey-Ewing A, Kennedy MB, Carter R, Cosenza SC, Soprano KJ, Lian JB, Stein JL, Stein GS (1990). Science 247, 1454-1457 [pdf]

Modifications of protein-DNA interactions in the proximal promoter of a cell-growth-related histone gene during onset and progression of osteoblast differenti­ation. Owen TA, Holthuis JC, Markose E, van Wijnen AJ, Wolfe SA, Grimes SR, Lian JB, Stein GS (1990) Proc. Natl. Acad. Sci. USA 87, 5129-5133 [pdf]

Nerve growth factor-induced changes in the intracellular localization of the Protein Kinase C substrate B-50 in pheochromocy­toma PC12 cells. Van Hooff CAM, Holthuis JC, Oestreicher AB, Boonstra J, de Graan PNE, Gispen WH (1989) J. Cell Biol. 108:1115-1125 [pdf]

Production of insulin-like growth factors, platelet-derived growth factor, and transforming growth factors and their role in the density-dependent growth regulation of a differentiated embryonal carcinoma cell line. Van Zoelen EJJ, Koornneef I, Holthuis JC, Ward-van Oostwaard ThMJ, Feijen A, de Poorter TL, Mummery CL, van Buul-Offers SC (1989) Endocrinol. 124, 2029-2041 [pdf]