Recruitment of LC3 to Damaged Golgi Apparatus
Cell Death & Differentiation (2019) 26:1467–1484 https://doi.org/10.1038/s41418-018-0221-5 ARTICLE Recruitment of LC3 to damaged Golgi apparatus 1,2,3 4 2,3 2,3 5,6 Lígia C. Gomes-da-Silva ● Ana Joaquina Jimenez ● Allan Sauvat ● Wei Xie ● Sylvie Souquere ● 4 7 8,9 8,9 1 2,3 Séverine Divoux ● Marko Storch ● Baldur Sveinbjørnsson ● Øystein Rekdal ● Luis G. Arnaut ● Oliver Kepp ● 2,3,10,11,12,13 4 Guido Kroemer ● Franck Perez Received: 11 May 2018 / Accepted: 8 October 2018 / Published online: 22 October 2018 © ADMC Associazione Differenziamento e Morte Cellulare 2018 Abstract LC3 is a protein that can associate with autophagosomes, autolysosomes, and phagosomes. Here, we show that LC3 can also redistribute toward the damaged Golgi apparatus where it clusters with SQSTM1/p62 and lysosomes. This organelle-specific relocation, which did not involve the generation of double-membraned autophagosomes, could be observed after Golgi damage was induced by various strategies, namely (i) laser-induced localized cellular damage, (ii) local expression of peroxidase and exposure to peroxide and diaminobenzidine, (iii) treatment with the Golgi-tropic photosensitizer redaporfin and light, (iv) or exposure to the Golgi-tropic anticancer peptidomimetic LTX-401. Mechanistic exploration led to the conclusion that both reactive oxygen species-dependent and -independent Golgi damage induces a similar phenotype that 1234567890();,: 1234567890();,: depended on ATG5 yet did not depend on phosphatidylinositol-3-kinase catalytic subunit type 3 and Beclin-1. Interestingly, knockout of ATG5 sensitized cells to Golgi damage-induced cell death, suggesting that the pathway culminating in the relocation of LC3 to the damaged Golgi may have a cytoprotective function.
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