{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:19:50Z","timestamp":1792113590693,"version":"4.4.0"},"reference-count":37,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CIBERER\/ISCIII","award":["ACCI 2019"],"award-info":[{"award-number":["ACCI 2019"]}]},{"name":"CIBERER\/ISCIII","award":["PID2019-108578RB-I00"],"award-info":[{"award-number":["PID2019-108578RB-I00"]}]},{"name":"CIBERER\/ISCIII","award":["2017SGR-0738"],"award-info":[{"award-number":["2017SGR-0738"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n\/FEDER","award":["ACCI 2019"],"award-info":[{"award-number":["ACCI 2019"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n\/FEDER","award":["PID2019-108578RB-I00"],"award-info":[{"award-number":["PID2019-108578RB-I00"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n\/FEDER","award":["2017SGR-0738"],"award-info":[{"award-number":["2017SGR-0738"]}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["ACCI 2019"],"award-info":[{"award-number":["ACCI 2019"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["PID2019-108578RB-I00"],"award-info":[{"award-number":["PID2019-108578RB-I00"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2017SGR-0738"],"award-info":[{"award-number":["2017SGR-0738"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mutations in the Ceramide Kinase-like (CERKL) gene cause retinal dystrophies, characterized by progressive degeneration of retinal neurons, which eventually lead to vision loss. Among other functions, CERKL is involved in the regulation of autophagy, mitochondrial dynamics, and metabolism in the retina. However, CERKL is nearly ubiquitously expressed, and it has been recently described to play a protective role against brain injury. Here we show that Cerkl is expressed in the hippocampus, and we use mouse hippocampal neurons to explore the impact of either overexpression or depletion of CERKL on mitochondrial trafficking and dynamics along axons. We describe that a pool of CERKL localizes at mitochondria in hippocampal axons. Importantly, the depletion of CERKL in the CerklKD\/KO mouse model is associated with changes in the expression of fusion\/fission molecular regulators, induces mitochondrial fragmentation, and impairs axonal mitochondrial trafficking. Our findings highlight the role of CERKL, a retinal dystrophy gene, in the regulation of mitochondrial health and homeostasis in central nervous system anatomic structures other than the retina.<\/jats:p>","DOI":"10.3390\/ijms231911593","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T22:19:27Z","timestamp":1665267567000},"page":"11593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["CERKL, a Retinal Dystrophy Gene, Regulates Mitochondrial Transport and Dynamics in Hippocampal Neurons"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2001-6814","authenticated-orcid":false,"given":"Roc\u00edo","family":"Garc\u00eda-Arroyo","sequence":"first","affiliation":[{"name":"Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain"},{"name":"CIBERER, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Institut de Biomedicina-Institut de Recerca Sant Joan de D\u00e9u (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7941-983X","authenticated-orcid":false,"given":"Gemma","family":"Marfany","sequence":"additional","affiliation":[{"name":"Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain"},{"name":"CIBERER, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Institut de Biomedicina-Institut de Recerca Sant Joan de D\u00e9u (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain"},{"name":"DBGen Ocular Genomics, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Mirra","sequence":"additional","affiliation":[{"name":"Department of Genetics, Microbiology and Statistics, Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain"},{"name":"CIBERER, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Institut de Biomedicina-Institut de Recerca Sant Joan de D\u00e9u (IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2174\/1872312814666211210111820","article-title":"Physiological and Pathophysiological Role of Cysteine Metabolism in Human Metabolic Syndrome","volume":"14","author":"Muthuraman","year":"2021","journal-title":"Drug Metab. Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/978-3-030-27378-1_84","article-title":"Mitochondrial Gymnastics in Retinal Cells: A Resilience Mechanism Against Oxidative Stress and Neurodegeneration","volume":"Volume 1185","author":"Mirra","year":"2019","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"654785","DOI":"10.3389\/fnins.2021.654785","article-title":"Mitochondrial Dynamics: A Key Role in Neurodegeneration and a Potential Target for Neurodegenerative Disease","volume":"15","author":"Yang","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nrneurol.2012.227","article-title":"The retina as a window to the brain\u2014From eye research to CNS disorders","volume":"9","author":"London","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5944","DOI":"10.1167\/iovs.09-3982","article-title":"CERKL mutations cause an autosomal recessive cone-rod dystrophy with inner retinopathy","volume":"50","author":"Aleman","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5202","DOI":"10.1167\/iovs.10-7101","article-title":"High transcriptional complexity of the retinitis pigmentosa CERKL gene in human and mouse","volume":"52","author":"Garanto","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","first-page":"168","article-title":"Overexpression of CERKL, a gene responsible for retinitis pigmentosa in humans, protects cells from apoptosis induced by oxidative stress","volume":"15","author":"Tuson","year":"2009","journal-title":"Mol.Vis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.exer.2013.03.003","article-title":"Specific sphingolipid content decrease in Cerkl knockdown mouse retinas","volume":"110","author":"Garanto","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1167\/iovs.12-9770","article-title":"Ceramide kinase-like (CERKL) interacts with neuronal calcium sensor proteins in the retina in a cation-dependent manner","volume":"53","author":"Nevet","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1080\/15548627.2018.1520548","article-title":"CERKL regulates autophagy via the NAD-dependent deacetylase SIRT1","volume":"15","author":"Hu","year":"2019","journal-title":"Autophagy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105405","DOI":"10.1016\/j.nbd.2021.105405","article-title":"CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina","volume":"156","author":"Mirra","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.bbadis.2014.04.009","article-title":"CERKL interacts with mitochondrial TRX2 and protects retinal cells from oxidative stress-induced apoptosis","volume":"1842","author":"Li","year":"2014","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Arroyo, R., Gavald\u00e0, A., Villarroya, F., Marfany, G., and Mirra, S. (2021). Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria from Oxidative Stress Effects. Antioxidants, 10.","DOI":"10.3390\/antiox10122018"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/bjd.19753","article-title":"CERKL is upregulated in cutaneous squamous cell carcinoma and maintains cellular sphingolipids and resistance to oxidative stress","volume":"185","author":"Meyer","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1515\/hsz-2021-0411","article-title":"CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1\/PINK1\/Parkin pathway and mitophagy induction","volume":"403","author":"Huang","year":"2022","journal-title":"Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1167\/iovs.61.8.14","article-title":"A New Cerkl Mouse Model Generated by CRISPR-Cas9 Shows Progressive Retinal Degeneration and Altered Morphological and Electrophysiological Phenotype","volume":"61","author":"Andres","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nrn3156","article-title":"Mitochondrial transport in neurons: Impact on synaptic homeostasis and neurodegeneration","volume":"13","author":"Sheng","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/jnr.24411","article-title":"Mechanisms for the maintenance and regulation of axonal energy supply","volume":"97","author":"Chamberlain","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/nrm2275","article-title":"Functions and dysfunctions of mitochondrial dynamics","volume":"8","author":"Detmer","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1086\/381055","article-title":"Mutation of CERKL, a Novel Human Ceramide Kinase Gene, Causes Autosomal Recessive Retinitis Pigmentosa (RP26)","volume":"74","author":"Tuson","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1002\/1873-3468.14298","article-title":"Mitochondria, energy, and metabolism in neuronal health and disease","volume":"596","author":"Trigo","year":"2022","journal-title":"FEBS Lett."},{"key":"ref_22","first-page":"a011304","article-title":"Mitochondrial trafficking in neurons","volume":"5","author":"Schwarz","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.tcb.2009.11.002","article-title":"Control of mitochondrial transport and localization in neurons","volume":"20","author":"MacAskill","year":"2010","journal-title":"Trends Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"31462","DOI":"10.1038\/srep31462","article-title":"Mfn2 is required for mitochondrial development and synapse formation in human induced pluripotent stem cells\/hiPSC derived cortical neurons","volume":"6","author":"Fang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1074\/jbc.M115.699447","article-title":"DISC1-dependent regulation of mitochondrial dynamics controls the morphogenesis of complex neuronal dendrites","volume":"291","author":"Norkett","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1093\/hmg\/ddt319","article-title":"The ALS disease-associated mutant TDP-43 impairs mitochondrial dynamics and function in motor neurons","volume":"22","author":"Wang","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1163","DOI":"10.1038\/cddis.2014.121","article-title":"The Armc10\/SVH gene: Genome context, regulation of mitochondrial dynamics and protection against A\u03b2-induced mitochondrial fragmentation","volume":"5","author":"Serrat","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"A\u00edsa-Mar\u00edn, I., Garc\u00eda-Arroyo, R., Mirra, S., and Marfany, G. (2021). The alter retina: Alternative splicing of retinal genes in health and disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041855"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.conb.2019.01.015","article-title":"Surveillance and transportation of mitochondria in neurons","volume":"57","author":"Vanhauwaert","year":"2019","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/sj.cdd.4401260","article-title":"Dynamics of mitochondrial morphology in healthy cells and during apoptosis","volume":"10","author":"Karbowski","year":"2003","journal-title":"Cell Death Differ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111212","DOI":"10.1016\/j.mad.2020.111212","article-title":"Mitochondrial fission and fusion: A dynamic role in aging and potential target for age-related disease","volume":"186","author":"Liu","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.molcel.2016.01.028","article-title":"The Mitochondrial Basis of Aging","volume":"61","author":"Sun","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2017.04.018","article-title":"Development or disease: Duality of the mitochondrial permeability transition pore","volume":"426","author":"Quintanilla","year":"2017","journal-title":"Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fathinajafabadi, A., P\u00e9rez-Jim\u00e9nez, E., Riera, M., Knecht, E., and Gonz\u00e0lez-Duarte, R. (2014). CERKL, a retinal disease gene, encodes an mRNA-binding protein that localizes in compact and untranslated mRNPs associated with microtubules. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087898"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41583-018-0091-3","article-title":"Mitochondria as central regulators of neural stem cell fate and cognitive function","volume":"20","author":"Khacho","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kim, J.M., Kim, H.G., and Son, C.G. (2018). Tissue-Specific Profiling of Oxidative Stress-Associated Transcriptome in a Healthy Mouse Model. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103174"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1016\/j.bbadis.2015.06.025","article-title":"Cdk5-mediated mitochondrial fission: A key player in dopaminergic toxicity in Huntington\u2019s disease","volume":"1852","author":"Cherubini","year":"2015","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11593\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:44:51Z","timestamp":1760143491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,30]]},"references-count":37,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911593"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911593","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,30]]}}}