Sulfide quinone oxidoreductase contributes to voltage sensing of the mitochondrial permeability transition pore.
Sqor
coenzyme Q
mitochondria
permeability transition pore
proton leak
sulfide quinone oxidoreductase
ubiquinone
voltage regulator
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
29 Feb 2024
29 Feb 2024
Historique:
revised:
18
12
2023
received:
26
06
2023
accepted:
02
02
2024
medline:
20
2
2024
pubmed:
20
2
2024
entrez:
20
2
2024
Statut:
ppublish
Résumé
Pathological opening of the mitochondrial permeability transition pore (mPTP) is implicated in the pathogenesis of many disease processes such as myocardial ischemia, traumatic brain injury, Alzheimer's disease, and diabetes. While we have gained insight into mPTP biology over the last several decades, the lack of translation of this knowledge into successful clinical therapies underscores the need for continued investigation and use of different approaches to identify novel regulators of the mPTP with the hope of elucidating new therapeutic targets. Although the mPTP is known to be a voltage-gated channel, the identity of its voltage sensor remains unknown. Here we found decreased gating potential of the mPTP and increased expression and activity of sulfide quinone oxidoreductase (SQOR) in newborn Fragile X syndrome (FXS) mouse heart mitochondria, a model system of coenzyme Q excess and relatively decreased mPTP open probability. We further found that pharmacological inhibition and genetic silencing of SQOR increased mPTP open probability in vitro in adult murine cardiac mitochondria and in the isolated-perfused heart, likely by interfering with voltage sensing. Thus, SQOR is proposed to contribute to voltage sensing by the mPTP and may be a component of the voltage sensing apparatus that modulates the gating potential of the mPTP.
Identifiants
pubmed: 38376922
doi: 10.1096/fj.202301280R
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23494Subventions
Organisme : HHS | NIH | National Institute of General Medical Sciences (NIGMS)
ID : T32GM008464
Organisme : HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
ID : R01NS112706
Organisme : Society of Pediatric Anesthesia Young Investigator Research Award
Organisme : Columbia University Irving Medical Center Target of Opportunity Provost award
Informations de copyright
© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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