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

Nazarko TY, Ozeki K, Till A, Ramakrishnan G, Lotfi P, Yan M, Subramani S - J. Cell Biol. (2014)

Bottom Line: Palmitoyl-CoA competes with Atg30 for Atg37 binding.The human orthologue of Atg37, acyl-CoA-binding domain containing protein 5 (ACBD5), is also peroxisomal and is required specifically for pexophagy.We suggest that Atg37/ACBD5 is a new component and positive regulator of the pexophagic RPC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Molecular Biology, Division of Biological Sciences, and 2 San Diego Center for Systems Biology, University of California, San Diego, La Jolla, CA 92093.

ABSTRACT
Autophagy is a membrane trafficking pathway that sequesters proteins and organelles into autophagosomes. The selectivity of this pathway is determined by autophagy receptors, such as the Pichia pastoris autophagy-related protein 30 (Atg30), which controls the selective autophagy of peroxisomes (pexophagy) through the assembly of a receptor protein complex (RPC). However, how the pexophagic RPC is regulated for efficient formation of the phagophore, an isolation membrane that sequesters the peroxisome from the cytosol, is unknown. Here we describe a new, conserved acyl-CoA-binding protein, Atg37, that is an integral peroxisomal membrane protein required specifically for pexophagy at the stage of phagophore formation. Atg30 recruits Atg37 to the pexophagic RPC, where Atg37 regulates the recruitment of the scaffold protein, Atg11. Palmitoyl-CoA competes with Atg30 for Atg37 binding. The human orthologue of Atg37, acyl-CoA-binding domain containing protein 5 (ACBD5), is also peroxisomal and is required specifically for pexophagy. We suggest that Atg37/ACBD5 is a new component and positive regulator of the pexophagic RPC.

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Overexpression of Atg37 does not interfere with pexophagy. (A and B) Overexpression of Atg37 does not induce pexophagy (A) or affect the growth of cells in methanol medium (B). The data shown in B are from a single representative experiment out of two repeats. Ee, endogenous expression; Oe, overexpression. (C) Overexpression of neither N-terminal (GFP-Atg37) nor C-terminal (Atg37-GFP) fusions of Atg37 and GFP affects pexophagy. Methanol-grown cells were adapted to ethanol medium without nitrogen (SE-N). (D) Overexpression of Atg37 does not interfere with micropexophagy and macropexophagy. Cells were replica plated from methanol to glucose and ethanol plates, respectively. The residual activity of AOX was used to assess pexophagy.
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fig4: Overexpression of Atg37 does not interfere with pexophagy. (A and B) Overexpression of Atg37 does not induce pexophagy (A) or affect the growth of cells in methanol medium (B). The data shown in B are from a single representative experiment out of two repeats. Ee, endogenous expression; Oe, overexpression. (C) Overexpression of neither N-terminal (GFP-Atg37) nor C-terminal (Atg37-GFP) fusions of Atg37 and GFP affects pexophagy. Methanol-grown cells were adapted to ethanol medium without nitrogen (SE-N). (D) Overexpression of Atg37 does not interfere with micropexophagy and macropexophagy. Cells were replica plated from methanol to glucose and ethanol plates, respectively. The residual activity of AOX was used to assess pexophagy.

Mentions: Because overexpression of Atg30 induces pexophagy even under peroxisome proliferation conditions and slows down the growth of cells (Farré et al., 2008), we tested whether Atg37 behaved similarly. Overexpression of Atg37-GFP from the promoter of the GAPDH gene neither induced pexophagy, judged by the levels of Pex3 and Pex12 (Fig. 4 A), nor retarded the growth of cells (Fig. 4 B) in methanol medium.


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

Nazarko TY, Ozeki K, Till A, Ramakrishnan G, Lotfi P, Yan M, Subramani S - J. Cell Biol. (2014)

Overexpression of Atg37 does not interfere with pexophagy. (A and B) Overexpression of Atg37 does not induce pexophagy (A) or affect the growth of cells in methanol medium (B). The data shown in B are from a single representative experiment out of two repeats. Ee, endogenous expression; Oe, overexpression. (C) Overexpression of neither N-terminal (GFP-Atg37) nor C-terminal (Atg37-GFP) fusions of Atg37 and GFP affects pexophagy. Methanol-grown cells were adapted to ethanol medium without nitrogen (SE-N). (D) Overexpression of Atg37 does not interfere with micropexophagy and macropexophagy. Cells were replica plated from methanol to glucose and ethanol plates, respectively. The residual activity of AOX was used to assess pexophagy.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3926955&req=5

fig4: Overexpression of Atg37 does not interfere with pexophagy. (A and B) Overexpression of Atg37 does not induce pexophagy (A) or affect the growth of cells in methanol medium (B). The data shown in B are from a single representative experiment out of two repeats. Ee, endogenous expression; Oe, overexpression. (C) Overexpression of neither N-terminal (GFP-Atg37) nor C-terminal (Atg37-GFP) fusions of Atg37 and GFP affects pexophagy. Methanol-grown cells were adapted to ethanol medium without nitrogen (SE-N). (D) Overexpression of Atg37 does not interfere with micropexophagy and macropexophagy. Cells were replica plated from methanol to glucose and ethanol plates, respectively. The residual activity of AOX was used to assess pexophagy.
Mentions: Because overexpression of Atg30 induces pexophagy even under peroxisome proliferation conditions and slows down the growth of cells (Farré et al., 2008), we tested whether Atg37 behaved similarly. Overexpression of Atg37-GFP from the promoter of the GAPDH gene neither induced pexophagy, judged by the levels of Pex3 and Pex12 (Fig. 4 A), nor retarded the growth of cells (Fig. 4 B) in methanol medium.

Bottom Line: Palmitoyl-CoA competes with Atg30 for Atg37 binding.The human orthologue of Atg37, acyl-CoA-binding domain containing protein 5 (ACBD5), is also peroxisomal and is required specifically for pexophagy.We suggest that Atg37/ACBD5 is a new component and positive regulator of the pexophagic RPC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Molecular Biology, Division of Biological Sciences, and 2 San Diego Center for Systems Biology, University of California, San Diego, La Jolla, CA 92093.

ABSTRACT
Autophagy is a membrane trafficking pathway that sequesters proteins and organelles into autophagosomes. The selectivity of this pathway is determined by autophagy receptors, such as the Pichia pastoris autophagy-related protein 30 (Atg30), which controls the selective autophagy of peroxisomes (pexophagy) through the assembly of a receptor protein complex (RPC). However, how the pexophagic RPC is regulated for efficient formation of the phagophore, an isolation membrane that sequesters the peroxisome from the cytosol, is unknown. Here we describe a new, conserved acyl-CoA-binding protein, Atg37, that is an integral peroxisomal membrane protein required specifically for pexophagy at the stage of phagophore formation. Atg30 recruits Atg37 to the pexophagic RPC, where Atg37 regulates the recruitment of the scaffold protein, Atg11. Palmitoyl-CoA competes with Atg30 for Atg37 binding. The human orthologue of Atg37, acyl-CoA-binding domain containing protein 5 (ACBD5), is also peroxisomal and is required specifically for pexophagy. We suggest that Atg37/ACBD5 is a new component and positive regulator of the pexophagic RPC.

Show MeSH
Related in: MedlinePlus