PpAtg30 tags peroxisomes for turnover by selective autophagy.
Autophagy, an intrinsically nonselective process, can also target selective cargo for degradation. The mechanism of selective peroxisome turnover by autophagy-related processes (pexophagy), termed micropexophagy and macropexophagy, is unknown. We show how a Pichia pastoris protein, PpAtg30, mediates peroxisome selection during pexophagy. It is necessary for pexophagy, but not for other selective and nonselective autophagy-related processes. It localizes at the peroxisome membrane via interaction with peroxins, and during pexophagy it colocalizes transiently at the preautophagosomal structure (PAS) and interacts with the autophagy machinery. PpAtg30 is required for formation of pexophagy intermediates, such as the micropexophagy apparatus (MIPA) and the pexophagosome (Ppg). During pexophagy, PpAtg30 undergoes multiple phosphorylations, at least one of which is required for pexophagy. PpAtg30 overexpression stimulates pexophagy even under peroxisome-induction conditions, impairing peroxisome biogenesis. Therefore, PpAtg30 is a key player in the selection of peroxisomes as cargo and in their delivery to the autophagy machinery for pexophagy.
Farré
Jean-Claude
JC
Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, San Diego, CA 92093-0322, USA.
Manjithaya
Ravi
R
Mathewson
Richard D
RD
Subramani
Suresh
S
D001343:Autophagy / Q000502:physiology*; D001693:Biological Transport, Active; D003600:Cytosol / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D010766:Phosphorylation; D010843:Pichia / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism
D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D053402:PHEX Phosphate Regulating Neutral Endopeptidase