Peroxisomal Atg37 binds Atg30 or palmitoyl-CoA to regulate phagophore formation during pexophagy

Abstract

The acyl-CoA–binding protein Atg37 is a new component of the pexophagic receptor protein complex that regulates the recruitment of Atg11 by Atg30 in the peroxisomal membrane during pexophagy

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

“…In yeast the mechanism of recognition of specific cargo for both pexophagy and mitophagy is well understood. For methylotrophic yeasts (e.g., P. pastoris) the pexophagy receptor is Atg30, which interacts with peroxisomal membrane proteins Pex3, Pex14, and Atg37 (Till et al, 2012;Nazarko, 2014). However, for S. cerevisiae and related yeasts the pexophagy receptor is Atg36 and appears to interact solely with Pex3 (Motley et al, 2012).…”

“…Atg30 interacts also with Pex14, the scaffold protein Atg17, and the acyl-CoA binding protein Atg37 (Nazarko et al, 2014). The human ortholog of Atg37, acyl-CoA-binding domain containing protein 5 (ACBD5), is also peroxisomal and required for pexophagy (Nazarko et al, 2014). Despite their functional similarities Atg30 and Atg36 do not display any significant sequence homology and they are conserved only among a few yeast species.…”

“…A receptor protein complex (RPC) model has been proposed that encompasses the receptor protein as the key player that establishes interactions with ligands, scaffold, and phagophore proteins (Nazarko et al, 2014). The question remains which components of the RPC are involved in HIF-2α-driven pexophagy.…”

“…Pex3 acts as a docking station for several proteins involved in peroxisomal biogenesis and its interaction with Atg30 regulates the phosphorylation status of Atg30 by a yet unknown kinase . Atg30 interacts also with Pex14, the scaffold protein Atg17, and the acyl-CoA binding protein Atg37 (Nazarko et al, 2014). The human ortholog of Atg37, acyl-CoA-binding domain containing protein 5 (ACBD5), is also peroxisomal and required for pexophagy (Nazarko et al, 2014).…”

The life of the peroxisome: from birth to death

“…The P. pastoris integral PMP, Atg37, an acyl-CoA binding protein, also binds Pex3p and is recruited by Atg30 to the pexophagic receptor complex and binding to Atg30 and Acyl-CoA is competitive. The human Atg37 homologue, Abcd5, is also required for pexophagy [55]. Meanwhile in S. cerevisiae, Atg36 acts as an adapter between PEX3, ATG8 and ATG11 on the pre-autophagosomal structure, and ScPex14p is dispensable for pexophagy [56].…”