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. 2019 Jul 11;31(6):458–471. doi: 10.1089/ars.2018.7649

FIG. 2.

FIG. 2.

Selective autophagy related to p62. (A) Aggrephagy: CHIP and Parin are the major E3 ubiquitin ligase for protein aggregates. p62, NBR1, and ALFY enhance transport of polyubiquitinated proteins into autophagosome, and promote aggrephagy. (B) Pexophagy: The ubiquitination of PEX5 is mainly induced by the PEX2 E3 ubiquitin ligase. P62 and NBR1 mediate interaction of ubiquitinated peroxisomes and autophagosomes. (C) Mitophagy: PINK1 affects both of ubiquitin phosphorylation and Parkin E3 ubiquitin ligase activation. The mitochondrial deubiquitinase USP30 and phosphatase PTEN-L antagonize PINK1/Parkin-mediated ubiqutination. p62, NDP52, and OPTN are adaptors implicated in mitophagy. (D) (Left) Lysophagy: Galectins bind to exposed innermembrane glycosidase and recruit TRIM proteins. Unknown ubiqutinated lysosomal proteins and TRIM interact with p62 directly to promote lysophagy. (Right) Lipopagy: AUP1 recruits the Ube2g2 E2 ubiquitin conjugase. The LDs coated proteins PLIN2 and unknown ubiqutinated surface proteins can bind with p62 for the progression of lipophagy. Also, Rab7 small GTPase directly recruits LDs and Rab10 to the autophagosomal membrane by promoting interaction with the EHBP1 and EBDH2 complex on the autophagosome. ALFY, autophagy-linked FYVE protein; CHIP, c-terminus of heat shock chaperone 70-interacting protein; LDs, lipid droplets; NBR1, neighbor of BRCA gene 1; NDP52, nuclear dot protein 52kDa/calcium-binding and coiled-coil domain 2; OPTN, optineurin; PEX, peroxin; PINK1, PTEN-induced putative kinase 1; PLIN2, Perilipin 2; PTEN, phosphatase and tensin homolog; PTEN-L, PTEN-long.; USP, ubiquitin carboxyl-terminal hydrolase. Color images are available online.