Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin

Abstract

After bacterial invasion, ubiquitin is conjugated to host endosomal proteins and recognized by the autophagic machinery independent of LC3.

A current perspective of autophagosome biogenesis

“…In particular, the Atg16L1 complex must possess the ability to target substrates in a ULK1 complex-and Atg9-independent manner. Our recent finding that Atg16L1's C-terminal WD domain directly binds ubiquitin provides evidence for this [48]. Moreover, Atg16L1 was shown to directly bind the ULK1 complex subunit, FIP200, in this and two other studies [46,47].…”

“…Therefore, Atg12, Atg5, and Atg16(L1) are frequently used as markers for the early steps of autophagosome formation. The localization of the Atg12-Atg5-Atg16(L1) complex appears to be directed by Atg16(L1) [19,45], and it has been shown that mammalian Atg16L1 directly binds to the ULK1 complex subunit FIP200 [46][47][48]. In addition, the membrane-binding ability of yeast Atg5, which can be inhibited by Atg12 and activated by Atg16, has also been reported [49].…”

“…Recently, Koyama-Honda et al [69] have shown that ULK1 and Atg5 are simultaneously recruited and accumulate to form dots upon starvation, possibly through the direct interaction between FIP200 and Atg16L1 [46][47][48]. Shortly after ULK1/Atg5 dot formation, Atg14L accumulates to form a dot overlapping the ULK1/Atg5 dot, possibly through an association of ULK1 and Atg14L mediated by the Exo84 exocyst complex [70].…”

Ubiquitination of exposed glycoproteins by SCF FBXO27 directs damaged lysosomes for autophagy

“…Latex beads coated with transfection reagents induce endosome damage and are targeted by LC3 + autophagosomes after being endocytosed into the cell (15,20). We further determined whether FBXO27 was recruited to damaged endosomes in beadtransfected cells (Fig.…”

“…Furthermore, a key signaling step during mitophagy involves ubiquitination of outer membrane proteins of damaged mitochondria by the ubiquitin ligase Parkin, which is recruited from the cytoplasm by PINK1-mediated phosphorylation of ubiquitin (14). In another example, autophagy specifically targets invading bacteria to restrict their growth after ubiquitination (15). Furthermore, damaged lysosomes are selectively sequestered by autophagosomes through a ubiquitindependent mechanism called lysophagy (16,17).…”