Sulfide quinone oxidoreductase contributes to voltage sensing of the mitochondrial permeability transition pore

• DOI: 10.1096/fj.202301280r
• Publication Date: 2024-02-20T16:55:25Z
• Authors: Keren K. Griffiths; Aili Wang; Elizabeth A. Jonas; Richard J. Levy
• Keywords: MPTP; Voltage-dependent anion channel

Abstract Pathological opening of the mitochondrial permeability transition pore (mPTP) is implicated in pathogenesis many disease processes such as myocardial ischemia, traumatic brain injury, Alzheimer's disease, and diabetes. While we have gained insight into mPTP biology over last several decades, lack translation this knowledge successful clinical therapies underscores need for continued investigation use different approaches to identify novel regulators with hope elucidating new therapeutic targets. Although known be a voltage‐gated channel, identity its voltage sensor remains unknown. Here found decreased gating potential increased expression activity sulfide quinone oxidoreductase (SQOR) newborn Fragile X syndrome (FXS) mouse heart mitochondria, model system coenzyme Q excess relatively open probability. We further that pharmacological inhibition genetic silencing SQOR probability vitro adult murine cardiac mitochondria isolated‐perfused heart, likely by interfering sensing. Thus, proposed contribute sensing may component apparatus modulates mPTP.