Cell-Permeable Succinate Increases Mitochondrial Membrane Potential and Glycolysis in Leigh Syndrome Patient Fibroblasts
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Department of Biological Sciences, J. William Fulbright College of Arts and Sciences, University of Arkansas, Fayetteville, AR 72701, USA
2
Department of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR 72701, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Paolo Bernardi, Luca Scorrano and Gerardo Z. Lederkremer
Cells 2021, 10(9), 2255; https://doi.org/10.3390/cells10092255
Received: 15 July 2021
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Revised: 28 August 2021
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Accepted: 30 August 2021
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Published: 31 August 2021
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Organelle Function)
Mitochondrial disorders represent a large group of severe genetic disorders mainly impacting organ systems with high energy requirements. Leigh syndrome (LS) is a classic example of a mitochondrial disorder resulting from pathogenic mutations that disrupt oxidative phosphorylation capacities. Currently, evidence-based therapy directed towards treating LS is sparse. Recently, the cell-permeant substrates responsible for regulating the electron transport chain have gained attention as therapeutic agents for mitochondrial diseases. We explored the therapeutic effects of introducing tricarboxylic acid cycle (TCA) intermediate substrate, succinate, as a cell-permeable prodrug NV118, to alleviate some of the mitochondrial dysfunction in LS. The results suggest that a 24-hour treatment with prodrug NV118 elicited an upregulation of glycolysis and mitochondrial membrane potential while inhibiting intracellular reactive oxygen species in LS cells. The results from this study suggest an important role for TCA intermediates for treating mitochondrial dysfunction in LS. We show, here, that NV118 could serve as a therapeutic agent for LS resulting from mutations in mtDNA in complex I and complex V dysfunctions.
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MDPI and ACS Style
Bakare, A.B.; Rao, R.R.; Iyer, S. Cell-Permeable Succinate Increases Mitochondrial Membrane Potential and Glycolysis in Leigh Syndrome Patient Fibroblasts. Cells 2021, 10, 2255. https://doi.org/10.3390/cells10092255
AMA Style
Bakare AB, Rao RR, Iyer S. Cell-Permeable Succinate Increases Mitochondrial Membrane Potential and Glycolysis in Leigh Syndrome Patient Fibroblasts. Cells. 2021; 10(9):2255. https://doi.org/10.3390/cells10092255
Chicago/Turabian StyleBakare, Ajibola B., Raj R. Rao, and Shilpa Iyer. 2021. "Cell-Permeable Succinate Increases Mitochondrial Membrane Potential and Glycolysis in Leigh Syndrome Patient Fibroblasts" Cells 10, no. 9: 2255. https://doi.org/10.3390/cells10092255
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