Peroxisomal Atg37 binds Atg30 or palmitoyl-CoA to regulate phagophore formation during pexophagy
Open accessAbstract
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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RNAi-mediated knockdown of ACBD5 in HeLa cells reduced peroxisomal autophagy rates.
“While RNAi-mediated knockdown of ACBD5 in HeLa cells reduced peroxisomal autophagy rates (Nazarko et al., 2014), knockout of ACBD5 in HeLa and other mammalian cells did not affect pexophagy (Ferdinandusse et al., 2017; Kors et al., 2024).”
From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Nazarko et al., 2014
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“To explore this possibility, we performed the in vitro [14C]C16:0-CoA binding assay with increasing amounts of unlabeled C16:0-CoA or C24:0-CoA.”
BackgroundInfluentialTRIM37, a novel E3 ligase for PEX5-mediated peroxisomal matrix protein import
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- Authors
- Nazarko, T. Y., Ozeki, K., Till, A., Ramakrishnan, G., Lotfi, P., Yan, M., & Subramani, S.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Subramani, Suresh
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2014-02-17
- Volume
- 204
- Issue
- 4
- Pages
- 541-557
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC3926955
- OpenAlex
- W1981927394
- Cited by
- 99
- References
- 57
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 5 · 2020: 12 · 2019: 14 · 2018: 15 · 2017: 8 · 2016: 12 · 2015: 10 · 2014: 4
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (GM085764, GM069373)
- National Institute of General Medical Sciences (GM 085764, GM-069373, P50GM085764, R01GM069373)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK094843, DK094843)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- pexophagy, Atg11, phagophore formation, peroxisome degradation, selective autophagy, autophagy receptors, palmitoyl-CoA, acyl-CoA binding protein, peroxisomal membrane proteins
- MeSH terms
- Huntingtin Protein, Sequestosome-1 Protein, Autophagy, Fungal Proteins, HeLa Cells, Humans, Image Processing, Computer-Assisted, Membrane Proteins, Microscopy, Fluorescence, Mutation, Nerve Tissue Proteins, Palmitoyl Coenzyme A, Phagosomes, Pichia, Peroxisomes, Immunoprecipitation, Adaptor Proteins, Signal Transducing
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