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Events : CBAC Seminar: Mitochondrial ATP Production in Cardiac Cells

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Huyen (Gwen) Nguyen

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Cardiac Bioelectricity & Arrhythmia Center (CBAC), Dept. of Biomedical Engineering

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Type of Event

Scientific Seminar

Type of Lecture

Seminar Series

Start Time

2/9/2021 10:00 AM

End Time

2/9/2021 11:00 AM



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Cardiac Bioelectricity & Arrhythmia Center (CBAC)


W. Jonathan Lederer, MD-PhD

Speaker Affiliation

Director, Center for Biomedical Engineering and Technology
Professor of Physiology
University of Maryland School of Medicine


CBAC Seminar: Mitochondrial ATP Production in Cardiac Cells

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p>As part of the CBAC Seminar series, join us for this presentation by W. Jonathan Lederer, a Professor of Physiology & the Director of the Center For Biomedical Engineering & Technology, University of Maryland School of Medicine.

This seminar will be virtual. Register for this event by going here.

Abstract:  ATP production by mitochondria is crucial for multicellular life but remains poorly understood. We have investigated the molecular controls of this process in the heart and provide a new framework for its Ca2+-dependent regulation under physiological conditions. Specifically, we have identified three aspects of the process that are at odds with widely held beliefs:

First, while we agree that the entry of Ca2+ into the matrix is through the mitochondrial calcium uniporter (MCU) channels that reside in the inner mitochondrial membrane (IMM), the amount of Ca2+ that moves across the IMM is small. Furthermore, the properties of the MCU in heart provide direct evidence that neither its gating is nor "threshold" to conduct depend on extramitochondrial Ca2+. Finally, the number of MCU channels that are open is constant over the full physiological range of cytosolic [Ca2+]i. 

Second, matrix [Ca2+]m only acts at two regulatory sites in the matrix under simple physiological conditions and these sites are outside of the direct Krebs cycle pathway.  However, the action of [Ca2+]m serves to regulate the Krebs cycle production of NADH by regulating entry of substrate into the Krebs cycle.  It is the [NADH] that regulates the voltage across the IMM, DYM, through its action on the ETC.  Importantly, no direct action of [Ca2+]m on the electron transport chain (ETC) complexes II, III, IV and V contributes to the process.

Third, DYM regulates ATP production due to the dependence of ATP synthase on voltage across the IMM.  We show for the first time what the voltage-dependence of the ATP synthase is and show that it is dramatically different from earlier "gold standards".  In sum, we provide a new understanding of voltage-energized calcium-sensitive ATP production by mitochondria. 

See Wescott et al. Nature Metabolism 2019.

For more information, contact Huyen (Gwen) Nguyen at

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Cardiac Bioelectricity & Arrhythmia Center (CBAC) -
Location:  Zoom


W. Jonathan Lederer, MD-PhD -
CBAC Seminar: Mitochondrial ATP Production in Cardiac Cells


Cardiac Bioelectricity & Arrhythmia Center (CBAC) -
Location:  Zoom -
W. Jonathan Lederer, MD-PhD -
CBAC Seminar: Mitochondrial ATP Production in Cardiac Cells





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Created at 12/28/2020 1:52 PM by  
Last modified at 12/29/2020 9:15 AM by Andrew Richards