Details

Autor(en) / Beteiligte

• Patel, Akshar
• Simkulet, Matthew
• Maity, Soumya
• Venkatesan, Manigandan
• Matzavinos, Anastasios
• Madesh, Muniswamy
• Alevriadou, B Rita

Titel

The mitochondrial Ca 2+ uniporter channel synergizes with fluid shear stress to induce mitochondrial Ca 2+ oscillations

Ist Teil von

• Scientific reports, 2022-12, Vol.12 (1), p.21161

Ort / Verlag

England

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• The mitochondrial calcium (Ca ) uniporter (MCU) channel is responsible for mitochondrial Ca influx. Its expression was found to be upregulated in endothelial cells (ECs) under cardiovascular disease conditions. Since the role of MCU in regulating cytosolic Ca homeostasis in ECs exposed to shear stress (SS) is unknown, we studied mitochondrial Ca dynamics (that is known to decode cytosolic Ca signaling) in sheared ECs. To understand cause-and-effect, we ectopically expressed MCU in ECs. A higher percentage of MCU-transduced ECs exhibited mitochondrial Ca 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 (ΔΨ ) flickers, and depended on activation of the mechanosensitive Piezo1 channel and the endothelial nitric oxide synthase (eNOS). A positive feedback loop composed of mitochondrial Ca uptake/mROS flashes/ΔΨ flickers and endoplasmic reticulum Ca 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.