[en] Noise overexposure causes oxidative stress, leading to auditory hair cell damage. Adaptive peroxisome proliferation involving pejvakin, a peroxisome-associated protein from the gasdermin family, has been shown to protect against this harmful oxidative stress. However, the role of pejvakin in peroxisome dynamics and homeostasis remains unclear. Here we show that sound overstimulation induces an early and rapid selective autophagic degradation of peroxisomes (pexophagy) in auditory hair cells from wild-type, but not pejvakin-deficient (Pjvk (-/-)), mice. Noise overexposure triggers recruitment of the autophagosome-associated protein MAP1LC3B (LC3B; microtubule-associated protein 1 light chain 3beta) to peroxisomes in wild-type, but not Pjvk (-/-), mice. We also show that pejvakin-LC3B binding involves an LC3-interacting region within the predicted chaperone domain of pejvakin. In transfected cells and in vivo transduced auditory hair cells, cysteine mutagenesis experiments demonstrated the requirement for both C328 and C343, the two cysteine residues closest to the C terminus of pejvakin, for reactive oxygen species-induced pejvakin-LC3B interaction and pexophagy. The viral transduction of auditory hair cells from Pjvk (-/-) mice in vivo with both Pjvk and Lc3b cDNAs completely restored sound-induced pexophagy, fully prevented the development of oxidative stress, and resulted in normal levels of peroxisome proliferation, whereas Pjvk cDNA alone yielded only a partial correction of the defects. Overall, our results demonstrate that pexophagy plays a key role in noise-induced peroxisome proliferation and identify defective pexophagy as a cause of noise-induced hearing loss. They suggest that pejvakin acts as a redox-activated pexophagy receptor/adaptor, thereby identifying a previously unknown function of gasdermin family proteins.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Defourny, Jean ; Institut Pasteur (Paris) > Neurosciences > Unité de Génétique et Physiologie de l'Audition
Aghaie, Alain; Institut de la Vision > Syndrome de Usher et Autres Atteintes Rétino-Cochléaires
Perfettini, Isabelle; Institut Pasteur (Paris) > Neurosciences > Unité de Génétique et Physiologie de l'Audition
Avan, Paul; Université d'Auvergne > Faculté de Médecine > Laboratoire de Biophysique Sensorielle
Delmaghani, Sedigheh; Institut Pasteur (Paris) > Neurosciences > Unité de Génétique et Physiologie de l'Audition
Petit, Christine; Institut Pasteur (Paris) > Neurosciences > Unité de Génétique et Physiologie de l'Audition
Language :
English
Title :
Pejvakin-mediated pexophagy protects auditory hair cells against noise-induced damage.
Publication date :
2019
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
0027-8424
eISSN :
1091-6490
Publisher :
National Academy of Sciences, Washington, United States - District of Columbia
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Delmaghani S, et al. (2015) Hypervulnerability to sound exposure through impaired adaptive proliferation of peroxisomes. Cell 163:894–906.
Ohlemiller KK, Wright JS, Dugan LL (1999) Early elevation of cochlear reactive oxygen species following noise exposure. Audiol Neurotol 4:229–236.
Walker CL, Pomatto LCD, Tripathi DN, Davies KJA (2018) Redox regulation of homeostasis and proteostasis in peroxisomes. Physiol Rev 98:89–115.
Delmaghani S, et al. (2006) Mutations in the gene encoding pejvakin, a newly identified protein of the afferent auditory pathway, cause DFNB59 auditory neuropathy. Nat Genet 38:770–778.
Kovacs SB, Miao EA (2017) Gasdermins: Effectors of pyroptosis. Trends Cell Biol 27: 673–684.
Shi J, et al. (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526:660–665.
Kayagaki N, et al. (2015) Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526:666–671.
Ding J, et al. (2016) Pore-forming activity and structural autoinhibition of the gasdermin family. Nature 535:111–116.
Rogers C, et al. (2017) Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death. Nat Commun 8:14128.
Op de Beeck K, et al. (2011) The DFNA5 gene, responsible for hearing loss and involved in cancer, encodes a novel apoptosis-inducing protein. Eur J Hum Genet 19: 965–973.
Kabeya Y, et al. (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728.
Tanida I (2011) Autophagosome formation and molecular mechanism of autophagy. Antioxid Redox Signal 14:2201–2214.
Shibata M, et al. (2013) Highly oxidized peroxisomes are selectively degraded via autophagy in Arabidopsis. Plant Cell 25:4967–4983.
Gauthier T, Claude-Taupin A, Delage-Mourroux R, Boyer-Guittaut M, Hervouet E (2015) Proximity ligation in situ assay is a powerful tool to monitor specific ATG protein interactions following autophagy induction. PLoS One 10:e0128701.
Söderberg O, et al. (2006) Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat Methods 3:995–1000.
Kim PK, Hailey DW, Mullen RT, Lippincott-Schwartz J (2008) Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc Natl Acad Sci USA 105:20567–20574.
Deosaran E, et al. (2013) NBR1 acts as an autophagy receptor for peroxisomes. J Cell Sci 126:939–952.
Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ (2015) The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 10:845–858.
Alemu EA, et al. (2012) ATG8 family proteins act as scaffolds for assembly of the ULK complex: Sequence requirements for LC3-interacting region (LIR) motifs. J Biol Chem 287:39275–39290.
Birgisdottir AB, Lamark T, Johansen T (2013) The LIR motif: Crucial for selective autophagy. J Cell Sci 126:3237–3247.
Le Guilloux V, Schmidtke P, Tuffery P (2009) Fpocket: An open source platform for ligand pocket detection. BMC Bioinformatics 10:168.
Conway ME, Lee C (2015) The redox switch that regulates molecular chaperones. Biomol Concepts 6:269–284.
Jang HH, et al. (2004) Two enzymes in one: Two yeast peroxiredoxins display oxidative stress-dependent switching from a peroxidase to a molecular chaperone function. Cell 117:625–635.
Wang C, et al. (2012) Human protein-disulfide isomerase is a redox-regulated chaperone activated by oxidation of domain a′. J Biol Chem 287:1139–1149.
Mujtaba G, Bukhari I, Fatima A, Naz S (2012) A p.C343S missense mutation in PJVK causes progressive hearing loss. Gene 504:98–101.
Zhang J, et al. (2015) ATM functions at the peroxisome to induce pexophagy in response to ROS. Nat Cell Biol 17:1259–1269.
Anding AL, Baehrecke EH (2017) Cleaning house: Selective autophagy of organelles. Dev Cell 41:10–22.
Apanasets O, et al. (2014) PEX5, the shuttling import receptor for peroxisomal matrix proteins, is a redox-sensitive protein. Traffic 15:94–103.
Ma C, Hagstrom D, Polley SG, Subramani S (2013) Redox-regulated cargo binding and release by the peroxisomal targeting signal receptor, Pex5. J Biol Chem 288:27220–27231.
Jiang L, Hara-Kuge S, Yamashita S, Fujiki Y (2015) Peroxin Pex14p is the key component for coordinated autophagic degradation of mammalian peroxisomes by direct binding to LC3-II. Genes Cells 20:36–49.
Lismont C, Nordgren M, Van Veldhoven PP, Fransen M (2015) Redox interplay between mitochondria and peroxisomes. Front Cell Dev Biol 3:35.
Cho DH, Kim YS, Jo DS, Choe SK, Jo EK (2018) Pexophagy: Molecular mechanisms and implications for health and diseases. Mol Cells 41:55–64.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.