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Gentamicin affects the bioenergetics of isolated mitochondria and collapses the mitochondrial membrane potential in cochlear sensory hair cells

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posted on 2023-06-21, 06:01 authored by Molly O'Reilly, Luke Young, Nerissa K Kirkwood, Guy Richardson, Corne Kros, Anthony Moore
Aminoglycoside 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 Neuroscience

ISSN

1662-5102

Publisher

Frontiers

Issue

a416

Volume

13

Page range

1-12

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Sussex Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2019-09-24

First Open Access (FOA) Date

2019-09-24

First Compliant Deposit (FCD) Date

2019-09-17

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