Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes

Delmaghani, Sedigheh; Defourny, Jean; Aghaie, Asadollah; Beurg, Maryline; Dulon, Didier; Thelen, Nicolas; Perfettini, Isabelle; Zelles, Tibor; Aller, Máté; Meyer, A.; Emptoz, Alice; Giraudet, Fabrice; Leibovici, Michel; Dartevelle, Sylvie; Soubigou, Guillaume; Thiry, Marc; Vizi, E.S.; Safieddine, Saaïd; Hardelin, Jean Pierre; Avan, Paul; Petit, Christine

doi:10.1016/j.cell.2015.10.023

Cited by 158 publications

(146 citation statements)

References 31 publications

(35 reference statements)

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“…In the interest of space, I will mainly focus on the three animal models in which the greatest extension in lifespan has been reported: C. elegans, D. melanogaster and M. musculus. For the same reason, I will not discuss ROS generated outside the mitochondrion, although it is clear that they can also contribute to the onset of aging and age-related disease [26,27]. For example, it has recently been shown that lifespan of the longlived clk-1 mutant worm is further extended by increasing mitochondrial ROS levels through knock-out of sod2 [28].…”

Section: Introductionmentioning

confidence: 96%

Mitochondrial reactive oxygen species: Do they extend or shorten animal lifespan?

Sanz

2016

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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Testing the predictions of the Mitochondrial Free Radical Theory of Ageing (MFRTA) has provided a deep understanding of the role of reactive oxygen species (ROS) and mitochondria in the aging process. However those data, which support MFRTA are in the majority correlative (e.g. increasing oxidative damage with age). In contrast the majority of direct experimental data contradict MFRTA (e.g. changes in ROS levels do not alter longevity as expected). Unfortunately, in the past, ROS measurements have mainly been performed using isolated mitochondria, a method which is prone to experimental artifacts and does not reflect the complexity of the in vivo process. New technology to study different ROS (e.g. superoxide or hydrogen peroxide) in vivo is now available; these new methods combined with state-of-the-art genetic engineering technology will allow a deeper interrogation of, where, when and how free radicals affect aging and pathological processes. In fact data that combine these new approaches, indicate that boosting mitochondrial ROS in lower animals is a way to extend both healthy and maximum lifespan. In this review, I discuss the latest literature focused on the role of mitochondrial ROS in aging, and how these new discoveries are helping to better understand the role of mitochondria in health and disease. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.

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Section: Introductionmentioning

confidence: 96%

Mitochondrial reactive oxygen species: Do they extend or shorten animal lifespan?

Sanz

2016

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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“…Electrophysiological whole-cell patchclamp recordings of hair cell mechanoelectrical transduction currents were carried out in cochlear explants from P8.5 mice, as described by Michalski et al (42). ABRs to sound stimuli were recorded and analyzed as previously described (43). The various tests to assess vestibular function were carried out as previously reported (34,35).…”

Section: Methodsmentioning

confidence: 99%

Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G

Emptoz

Michel

Lelli

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Our understanding of the mechanisms underlying inherited forms of inner ear deficits has considerably improved during the past 20 y, but we are still far from curative treatments. We investigated gene replacement as a strategy for restoring inner ear functions in a mouse model of Usher syndrome type 1G, characterized by congenital profound deafness and balance disorders. These mice lack the scaffold protein sans, which is involved both in the morphogenesis of the stereociliary bundle, the sensory antenna of inner ear hair cells, and in the mechanoelectrical transduction process. We show that a single delivery of the sans cDNA by the adenoassociated virus 8 to the inner ear of newborn mutant mice reestablishes the expression and targeting of the protein to the tips of stereocilia. The therapeutic gene restores the architecture and mechanosensitivity of stereociliary bundles, improves hearing thresholds, and durably rescues these mice from the balance defects. Our results open up new perspectives for efficient gene therapy of cochlear and vestibular disorders by showing that even severe dysmorphogenesis of stereociliary bundles can be corrected.gene | therapy | balance | mouse | Usher

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“…In recent years, some genes have been found to affect the susceptibility to noise in animal models [13, 14]. Several of the knockout mouse lines that have been developed, including Pjvk −/− [15], PMCA2 +/− [16], P2RX2 −/− [17], and CDH23 +/− [18], were determined to be more sensitive to noise than their wild type controls. Meanwhile, more studies are beginning to search for new NIHL susceptibility genes, and hundreds of single nucleotide polymorphism (SNP) loci have been found in genes involved in different pathways of the inner ear.…”

Section: Introductionmentioning

confidence: 99%

Loss of Myh14 Increases Susceptibility to Noise-Induced Hearing Loss in CBA/CaJ Mice

Zhang

Jin

et al. 2016

Neural Plasticity

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MYH14 is a member of the myosin family, which has been implicated in many motile processes such as ion-channel gating, organelle translocation, and the cytoskeleton rearrangement. Mutations in MYH14 lead to a DFNA4-type hearing impairment. Further evidence also shows that MYH14 is a candidate noise-induced hearing loss (NIHL) susceptible gene. However, the specific roles of MYH14 in auditory function and NIHL are not fully understood. In the present study, we used CRISPR/Cas9 technology to establish a Myh14 knockout mice line in CBA/CaJ background (now referred to as Myh14−/− mice) and clarify the role of MYH14 in the cochlea and NIHL. We found that Myh14−/− mice did not exhibit significant hearing loss until five months of age. In addition, Myh14−/− mice were more vulnerable to high intensity noise compared to control mice. More significant outer hair cell loss was observed in Myh14−/− mice than in wild type controls after acoustic trauma. Our findings suggest that Myh14 may play a beneficial role in the protection of the cochlea after acoustic overstimulation in CBA/CaJ mice.

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Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes

Cited by 158 publications

References 31 publications

Mitochondrial reactive oxygen species: Do they extend or shorten animal lifespan?

Mitochondrial reactive oxygen species: Do they extend or shorten animal lifespan?

Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G

Loss of Myh14 Increases Susceptibility to Noise-Induced Hearing Loss in CBA/CaJ Mice

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