| Structural highlights
Function
[ATG32_YEAST] Mitophagy-specific receptor that recruits the autophagic machinery to mitochondria and regulates selective degradation of mitochondria. Mitophagy contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Recruits ATG11 to the surface of mitochondria. Promotes also autophagy-dependent peroxisome degradation.[1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
Mitochondria are targeted for degradation by mitophagy, a selective form of autophagy. In Saccharomyces cerevisiae, mitophagy is dependent on the autophagy receptor, Atg32, an outer mitochondrial membrane protein. Once activated, Atg32 recruits the autophagy machinery to mitochondria, facilitating mitochondrial capture in phagophores, the precursors to autophagosomes. However, the mechanism of Atg32 activation remains poorly understood. To investigate this crucial step in mitophagy regulation, we examined the structure of Atg32. We have identified a structured domain in Atg32 that is essential for the initiation of mitophagy, as it is required for the proteolysis of the C-terminal domain of Atg32 and the subsequent recruitment of Atg11. The solution structure of this domain was determined by NMR spectroscopy, revealing that Atg32 contains a previously undescribed pseudo-receiver (PsR) domain. Our data suggests that the PsR domain of Atg32 regulates Atg32 activation and the initiation of mitophagy.
A Pseudo-Receiver Domain in Atg32 is Required for Mitophagy.,Xia X, Katzenell S, Reinhart EF, Bauer KM, Pellegrini M, Ragusa MJ Autophagy. 2018 Jun 16. doi: 10.1080/15548627.2018.1472838. PMID:29909755[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Okamoto K, Kondo-Okamoto N, Ohsumi Y. A landmark protein essential for mitophagy: Atg32 recruits the autophagic machinery to mitochondria. Autophagy. 2009 Nov;5(8):1203-5. Epub 2009 Nov 13. PMID:19770589
- ↑ Okamoto K, Kondo-Okamoto N, Ohsumi Y. Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev Cell. 2009 Jul;17(1):87-97. PMID:19619494 doi:http://dx.doi.org/S1534-5807(09)00254-8
- ↑ Kanki T, Wang K, Cao Y, Baba M, Klionsky DJ. Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev Cell. 2009 Jul;17(1):98-109. PMID:19619495 doi:http://dx.doi.org/S1534-5807(09)00255-X
- ↑ Kanki T, Wang K, Baba M, Bartholomew CR, Lynch-Day MA, Du Z, Geng J, Mao K, Yang Z, Yen WL, Klionsky DJ. A genomic screen for yeast mutants defective in selective mitochondria autophagy. Mol Biol Cell. 2009 Nov;20(22):4730-8. Epub 2009 Sep 30. PMID:19793921 doi:http://dx.doi.org/E09-03-0225
- ↑ Mao K, Wang K, Zhao M, Xu T, Klionsky DJ. Two MAPK-signaling pathways are required for mitophagy in Saccharomyces cerevisiae. J Cell Biol. 2011 May 16;193(4):755-67. doi: 10.1083/jcb.201102092. PMID:21576396 doi:http://dx.doi.org/10.1083/jcb.201102092
- ↑ Sampaio-Marques B, Felgueiras C, Silva A, Rodrigues M, Tenreiro S, Franssens V, Reichert AS, Outeiro TF, Winderickx J, Ludovico P. SNCA (alpha-synuclein)-induced toxicity in yeast cells is dependent on sirtuin 2 (Sir2)-mediated mitophagy. Autophagy. 2012 Oct;8(10):1494-509. doi: 10.4161/auto.21275. Epub 2012 Aug 23. PMID:22914317 doi:http://dx.doi.org/10.4161/auto.21275
- ↑ Motley AM, Nuttall JM, Hettema EH. Pex3-anchored Atg36 tags peroxisomes for degradation in Saccharomyces cerevisiae. EMBO J. 2012 Jun 29;31(13):2852-68. doi: 10.1038/emboj.2012.151. Epub 2012 May, 29. PMID:22643220 doi:http://dx.doi.org/10.1038/emboj.2012.151
- ↑ Kurihara Y, Kanki T, Aoki Y, Hirota Y, Saigusa T, Uchiumi T, Kang D. Mitophagy plays an essential role in reducing mitochondrial production of reactive oxygen species and mutation of mitochondrial DNA by maintaining mitochondrial quantity and quality in yeast. J Biol Chem. 2012 Jan 27;287(5):3265-72. doi: 10.1074/jbc.M111.280156. Epub 2011 , Dec 7. PMID:22157017 doi:http://dx.doi.org/10.1074/jbc.M111.280156
- ↑ Kondo-Okamoto N, Noda NN, Suzuki SW, Nakatogawa H, Takahashi I, Matsunami M, Hashimoto A, Inagaki F, Ohsumi Y, Okamoto K. Autophagy-related protein 32 acts as autophagic degron and directly initiates mitophagy. J Biol Chem. 2012 Mar 23;287(13):10631-8. Epub 2012 Feb 3. PMID:22308029 doi:http://dx.doi.org/10.1074/jbc.M111.299917
- ↑ Xia X, Katzenell S, Reinhart EF, Bauer KM, Pellegrini M, Ragusa MJ. A Pseudo-Receiver Domain in Atg32 is Required for Mitophagy. Autophagy. 2018 Jun 16. doi: 10.1080/15548627.2018.1472838. PMID:29909755 doi:http://dx.doi.org/10.1080/15548627.2018.1472838
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