Evidence map›Paper›PMID 27500493›Full record

ArticleThe Journal of clinical investigation2016

Mitochondrial calcium uptake underlies ROS generation during aminoglycoside-induced hair cell death.

Robert Esterberg, Tor Linbo, Sarah B Pickett, Patricia Wu, Henry C Ou, Edwin W Rubel, David W Raible

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
9.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

99 citing papers in PubMed, 168 citations in OpenAlex.

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  17. SKOOTS: Skeleton-oriented object segmentation for mitochondria.bioRxiv : the preprint server for biology · 2025
    Article
  18. Article
  19. TNFAIP8L2 maintains hair cell function and regulates age-related hearing loss via mTORC1 signaling.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  20. The Role of Calcium Signaling in Sensorineural Hearing Loss.International journal of medical sciences · 2025
    Review

39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Robert Esterberg
Tor Linbo
Sarah B Pickett
Patricia Wu
Henry C Ou
Edwin W Rubel
David W Raible
University of Washington · USMerrill (United States) · USSeattle Children's Hospital · US

Funding

UNIVERSITY OF WASHINGTON RESEARCH CORE CENTERP30DC004661 · NIDCD · UNIVERSITY OF WASHINGTON · PI WERNER, LYNNE A. · 2000 to 2014
$11.1M
Genetics of Zebrafish Hair Cell ToxicityR01DC005987 · NIDCD · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 2003 to 2023
$9.8M
The role of intracellular calcium in ototoxin-mediated hair cell deathF32DC012244 · NIDCD · UNIVERSITY OF WASHINGTON · PI ESTERBERG, ROBERT · 2011 to 2012
$109k
NIDCD NIH HHS F32 DC012244NIDCD NIH HHS P30 DC004661NIDCD NIH HHS R01 DC005987
6 · The paper itself

Abstract

Exposure to aminoglycoside antibiotics can lead to the generation of toxic levels of reactive oxygen species (ROS) within mechanosensory hair cells of the inner ear that have been implicated in hearing and balance disorders. Better understanding of the origin of aminoglycoside-induced ROS could focus the development of therapies aimed at preventing this event. In this work, we used the zebrafish lateral line system to monitor the dynamic behavior of mitochondrial and cytoplasmic oxidation occurring within the same dying hair cell following exposure to aminoglycosides. The increased oxidation observed in both mitochondria and cytoplasm of dying hair cells was highly correlated with mitochondrial calcium uptake. Application of the mitochondrial uniporter inhibitor Ru360 reduced mitochondrial and cytoplasmic oxidation, suggesting that mitochondrial calcium drives ROS generation during aminoglycoside-induced hair cell death. Furthermore, targeting mitochondria with free radical scavengers conferred superior protection against aminoglycoside exposure compared with identical, untargeted scavengers. Our findings suggest that targeted therapies aimed at preventing mitochondrial oxidation have therapeutic potential to ameliorate the toxic effects of aminoglycoside exposure.

Indexed as

AminoglycosidesAnimalsCalciumCell DeathCytoplasmDisease Models, AnimalHair Cells, AuditoryLateral Line SystemMitochondriaOxidation-ReductionOxygenReactive Oxygen SpeciesTransgenesZebrafishAminoglycosidesCalciumOxygenReactive Oxygen Species

Identifiers

PMID27500493
PMCPMC5004972
OpenAlexW2483712829

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.