Recruitment of LC3 to damaged Golgi apparatus

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 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.

Cell death in photodynamic therapy: From oxidative stress to anti-tumor immunity

“…Even though GA recruitment of LC3 appears to occur by a non-canonical form of autophagy, this pathway is potentially cytoprotective as double KO of ATG5 and ATG7, prevented LC3 recruitment also sensitized cells to killing by redaporfin-PDT. [96] Similar results were described for other strategies with the ability to interfere with GA homeostasis. These strategies included laser-induced localized cellular damage, local expression of peroxidase with exposure to peroxide and diaminobenzidine, exposure to the Golgi-tropic anticancer peptidomimetic LTX-401 [96], to the unsaturated fatty acid oleate [97] or to squaramidebased synthetic chloride transporters [98].…”

Tumor lysis with LTX-401 creates anticancer immunity

“…We have been characterizing the mode of action of several oncolytic reagents of this class such as LTX-315, LTX-401, DTT-205 and DTT-304. LTX-315 turned out to preferentially target mitochondrial membranes; 3,4 while LTX-401 destroys Golgi apparatus-associated membranes, [5][6][7] thus setting off a different cell-destroying cascade. 7 DTT-205 and DTT-304, instead, have a tropism for lysosomal membranes, thus activating yet another cell death subroutine.…”

Photothermal Killing of A549 Cells and Autophagy Induction by Bismuth Selenide Particles

“…Microtubule-associated protein 1 light chain 3 (LC3) is a signature protein of autophagy, composed of cytoplasmic LC3 (LC3-I) and LC3-II spotted on the membrane of autophagosomes [ 29 ]. The conversion of LC3 protein from LC3-I to LC3-II is widely recognized as an indicator of autophagy behavior [ 55 ]. Autophagy induced by the photothermal effect of Bi 2 Se 3 was also confirmed by an increased ratio of LC3-II/LC3-I.…”