Browsing by Author "Patel, Akshar"

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    The mitochondrial Ca2+ uniporter channel synergizes with fluid shear stress to induce mitochondrial Ca2+ oscillations
    (2022) Patel, Akshar; Simkulet, Matthew; Maity, Soumya; Venkatesan, Manigandan; Matzavinos, Anastasios; Madesh, Muniswamy; Alevriadou, B. Rita
    The mitochondrial calcium (Ca2+) uniporter (MCU) channel is responsible for mitochondrial Ca2+ influx. Its expression was found to be upregulated in endothelial cells (ECs) under cardiovascular disease conditions. Since the role of MCU in regulating cytosolic Ca2+ homeostasis in ECs exposed to shear stress (SS) is unknown, we studied mitochondrial Ca2+ dynamics (that is known to decode cytosolic Ca2+ signaling) in sheared ECs. To understand cause-and-effect, we ectopically expressed MCU in ECs. A higher percentage of MCU-transduced ECs exhibited mitochondrial Ca2+ transients/oscillations, and at higher frequency, under SS compared to sheared control ECs. Transients/oscillations correlated with mitochondrial reactive oxygen species (mROS) flashes and mitochondrial membrane potential (Delta Psi(m)) flickers, and depended on activation of the mechanosensitive Piezo1 channel and the endothelial nitric oxide synthase (eNOS). A positive feedback loop composed of mitochondrial Ca2+ uptake/mROS flashes/Delta Psi(m) flickers and endoplasmic reticulum Ca2+ release, in association with Piezo1 and eNOS, provided insights into the mechanism by which SS, under conditions of high MCU activity, may shape vascular EC energetics and function.