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Gentamicin affects the bioenergetics of isolated mitochondria and collapses the mitochondrial membrane potential in cochlear sensory hair cells
journal contribution
posted on 2023-06-21, 06:01 authored by Molly O'Reilly, Luke Young, Nerissa K Kirkwood, Guy Richardson, Corne Kros, Anthony MooreAminoglycoside antibiotics are widely prescribed to treat a variety of serious bacterial infections. They are extremely useful clinical tools, but have adverse side effects such as oto- and nephrotoxicity. Once inside a cell they are thought to cause mitochondrial dysfunction, subsequently leading to apoptotic cell death due to an increase in reactive oxygen species (ROS) production. Here we present evidence of a direct effect of gentamicin (the most commonly prescribed aminoglycoside) on the respiratory activities of isolated rat liver and kidney mitochondria. We show that gentamicin stimulates state 4 and inhibits state 3u respiratory rates, thereby reducing the respiratory control ratio (RCR) whilst simultaneously causing a collapse of the mitochondrial membrane potential (MtMP). We propose that gentamicin behaves as an uncoupler of the electron transport chain (ETC) – a hypothesis supported by our evidence that it reduces the production of mitochondrial ROS (MtROS). We also show that gentamicin collapses the MtMP in the sensory hair cells (HCs) of organotypic mouse cochlear cultures.
Funding
Mechanisms of aminoglyscoside ototoxicity and drug damage repair in sensory hair cells: towards the design of otoprotective strategies.; G1025; MRC-MEDICAL RESEARCH COUNCIL; MR/K005561/1
A commercial plan for the exploitation of a series of novel anti-AOX compounds and associated technology applications; G2763; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/T003200/1
History
Publication status
- Published
File Version
- Published version
Journal
Frontiers in Cellular NeuroscienceISSN
1662-5102Publisher
FrontiersExternal DOI
Issue
a416Volume
13Page range
1-12Department affiliated with
- Biochemistry Publications
Research groups affiliated with
- Sussex Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2019-09-24First Open Access (FOA) Date
2019-09-24First Compliant Deposit (FCD) Date
2019-09-17Usage metrics
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