{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:48:42Z","timestamp":1790999322475,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,8,26]],"date-time":"2014-08-26T00:00:00Z","timestamp":1409011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"DFG","award":["DFG FOR 926"],"award-info":[{"award-number":["DFG FOR 926"]}]},{"name":"Peter and Beate Heller Foundation"},{"DOI":"10.13039\/100016021","name":"Corona Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016021","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cannabinoid Receptor 1 (CB1) has been initially described as the receptor for Delta\u20109\u2010Tetrahydrocannabinol in the central nervous system (CNS), mediating retrograde synaptic signaling of the endocannabinoid system. Beside its expression in various CNS regions, CB1 is ubiquituous in peripheral tissues, where it mediates, among other activities, the cell's energy homeostasis. We sought to examine the role of CB1 in the context of the evolutionarily conserved autophagic machinery, a main constituent of the regulation of the intracellular energy status. Manipulating CB1 by siRNA knockdown in mammalian cells caused an elevated autophagic flux, while the expression of autophagy\u2010related genes remained unaltered. Pharmacological inhibition of CB1 activity using Rimonabant likewise caused an elevated autophagic flux, which was independent of the mammalian target of rapamycin complex 1, a major switch in the control of canonical autophagy. In addition, knocking down coiled\u2010coil myosin\u2010like BCL2\u2010interacting protein 1, the key\u2010protein of the second canonical autophagy control complex, was insufficient to reduce the elevated autophagic flux induced by Rimonabant. Interestingly, lysosomal activity is not altered, suggesting a specific effect of CB1 on the regulation of autophagic flux. We conclude that CB1 activity affects the autophagic flux independently of the two major canonic regulation complexes controlling autophagic vesicle formation.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12839-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><jats:p>Regulation of the autophagic flux in certain physiological situations such as an imbalance of nutrient supply as well as in pathological stages is of major importance for neuronal and non\u2010neuronal cells. CB1 (Cannabinoid receptor 1) affects the metabolism of cells directly. In this study, we provide evidence that CB1 signaling has a direct influence on autophagy which might help the cell to find the right adjustment to different metabolic states and CB1 activity exerts its modulatory action independent of the canonical mTOR\u2010 and BECLIN1\u2010complexes regulating autophagy.<\/jats:p>","DOI":"10.1111\/jnc.12839","type":"journal-article","created":{"date-parts":[[2014,7,28]],"date-time":"2014-07-28T09:57:43Z","timestamp":1406541463000},"page":"484-497","source":"Crossref","is-referenced-by-count":43,"title":["Cannabinoid receptor 1 modulates the autophagic flux independent of mTOR\u2010 and BECLIN1\u2010complex"],"prefix":"10.1111","volume":"131","author":[{"given":"Christof","family":"Hiebel","sequence":"first","affiliation":[{"name":"Institute for Pathobiochemistry University Medical Center Johannes Gutenberg University Mainz Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Kromm","sequence":"additional","affiliation":[{"name":"Institute for Pathobiochemistry University Medical Center Johannes Gutenberg University Mainz Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Stark","sequence":"additional","affiliation":[{"name":"Institute for Pathobiochemistry University Medical Center Johannes Gutenberg University Mainz Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Behl","sequence":"additional","affiliation":[{"name":"Institute for Pathobiochemistry University Medical Center Johannes Gutenberg University Mainz Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3053"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.217463"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.77904"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2006.12.038"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501707200"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.11.012"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3249"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17725"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.151"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0026-895X(25)09876-1","article-title":"Determination and characterization of a cannabinoid receptor in rat brain","volume":"34","author":"Devane W. A.","year":"1988","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2763"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1999.4683"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1196371"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05925"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1995.tb20780.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.29"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-011-0795-6"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2010.203"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(73)90163-3"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.07.035"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-6980(02)00060-6"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e08-01-0080"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030156"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.04.026"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.19496"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.01.021"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.511212"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/346561a0"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01092a065"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.12.004"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-092910-154005"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-012-8246-0"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/365061a0"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3232"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.162040"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12144"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1369.052"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200523057"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04642.x"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702824200"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.9.e36"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2013.08.001"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802583"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.7.9508"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI37948"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.05.027"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3482"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1115740"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2011.32"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-04-01398.2003"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/35069076"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn025"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1854"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20116"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.12839","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.12839","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.12839","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T23:31:26Z","timestamp":1746315086000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.12839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,26]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1111\/jnc.12839"],"URL":"https:\/\/doi.org\/10.1111\/jnc.12839","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,26]]}}}