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Regulatory pathways, involving post\u2010translational modifications such as phosphorylation, play a critical role in controlling this tightly orchestrated process. Here, we demonstrate that TBK1 regulates autophagy by phosphorylating autophagy modifiers LC3C and GABARAP\u2010L2 on surface\u2010exposed serine residues (LC3C S93 and S96; GABARAP\u2010L2 S87 and S88). This phosphorylation event impedes their binding to the processing enzyme ATG4 by destabilizing the complex. Phosphorylated LC3C\/GABARAP\u2010L2 cannot be removed from liposomes by ATG4 and are thus protected from ATG4\u2010mediated premature removal from nascent autophagosomes. This ensures a steady coat of lipidated LC3C\/GABARAP\u2010L2 throughout the early steps in autophagosome formation and aids in maintaining a unidirectional flow of the autophagosome to the lysosome. Taken together, we present a new regulatory mechanism of autophagy, which influences the conjugation and de\u2010conjugation of LC3C and GABARAP\u2010L2 to autophagosomes by TBK1\u2010mediated phosphorylation.<\/jats:p>","DOI":"10.15252\/embr.201948317","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T20:32:50Z","timestamp":1576873970000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["TBK1\u2010mediated phosphorylation of LC3C and GABARAP\u2010L2 controls autophagosome shedding by ATG4 protease"],"prefix":"10.1038","volume":"21","author":[{"given":"Lina","family":"Herhaus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramachandra M","family":"Bhaskara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alf H\u00e5kon","family":"Lystad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ux\u00eda","family":"Gestal\u2010Mato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Covarrubias\u2010Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Bonn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4711-7057","authenticated-orcid":false,"given":"Anne","family":"Simonsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-746X","authenticated-orcid":false,"given":"Gerhard","family":"Hummer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8156-9511","authenticated-orcid":false,"given":"Ivan","family":"Dikic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,11]]},"reference":[{"key":"BFEMBR201948317_CR1","doi-asserted-by":"crossref","first-page":"20170540","DOI":"10.1098\/rsbl.2017.0540","volume":"14","author":"W Xie","year":"2018","unstructured":"Xie W, Zhou J (2018) Aberrant regulation of autophagy in mammalian diseases. 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