Hi everyone,
Science at the Edge is resuming for the Fall semester over Zoom! We invite you to join us Friday Sept, 11 at 11:30 AM for the first Science at the Edge Online presentation.
Our speaker will be Dr. Jon Lederer from the University of Maryland. Talk details and Zoom invite follow.
Title: How mitochondrial ATP production is regulated in heart.
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.
Host: Jason Bazil ([log in to unmask]<mailto:[log in to unmask]>)
Alexander R Dickson is inviting you to a scheduled Zoom meeting.
Topic: Science at the Edge: Jon Lederer
Time: Sep 11, 2020 11:30 AM America/Detroit
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Meeting ID: 953 9503 7456
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Hope to see you there!
Alex
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Alex Dickson
Assistant Professor
Department of Biochemistry and Molecular Biology
Department of Computational Mathematics, Science and Engineering
Michigan State University
603 Wilson Rd, Office 310B
East Lansing, MI 48824
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