Details

Autor(en) / Beteiligte

• Das, Phonindra Nath
• Pedruzzi, Gabriele
• Bairagi, Nandadulal
• Chatterjee, Samrat

Titel

Coupling calcium dynamics and mitochondrial bioenergetic: an in silicostudy to simulate cardiomyocyte dysfunction

Ist Teil von

• Molecular bioSystems, 2016-02, Vol.12 (3), p.806-817

Erscheinungsjahr

2016

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The coupling of intracellular Ca super(2+) dynamics with mitochondrial bioenergetic is crucial for the functioning of cardiomyocytes both in healthy and disease conditions. The pathophysiological signature of the Cardiomyocyte Dysfunction (CD) is commonly related to decreased ATP production due to mitochondrial functional impairment and to an increased mitochondrial calcium content ([Ca super(2+)]m). These features advanced the therapeutic approaches which aim to reduce [Ca super(2+)]m. But whether [Ca super(2+)]m overload is the pathological trigger for CD or a physiological consequence, remained controversial. We addressed this issue in silicoand showed that [Ca super(2+)]m might not directly cause CD. Through model parameter recalibration, we demonstrated how mitochondria cope up with functionally impaired processes and consequently accumulate calcium. A strong coupling of the [Ca super(2+)]m oscillations with the ATP synthesis rate ensures robust calcium cycling and avoids CD. We suggested a cardioprotective role of the mitochondrial calcium uniporter and predicted that a mitochondrial sodium calcium exchanger could be a potential therapeutic target to restore the normal functioning of the cardiomyocyte.