Next Article in Journal
The Interplay between Glioblastoma and Its Microenvironment
Next Article in Special Issue
Circadian Organelles: Rhythms at All Scales
Previous Article in Journal
p27Kip1, an Intrinsically Unstructured Protein with Scaffold Properties
Previous Article in Special Issue
Regulation of the Phosphoinositide Code by Phosphorylation of Membrane Readers
 
 
Article

Cell-Permeable Succinate Increases Mitochondrial Membrane Potential and Glycolysis in Leigh Syndrome Patient Fibroblasts

1
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 / Revised: 28 August 2021 / Accepted: 30 August 2021 / 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. View Full-Text
Keywords: leigh syndrome; succinate prodrug; glycolysis; TCA cycle; mitochondrial respiration leigh syndrome; succinate prodrug; glycolysis; TCA cycle; mitochondrial respiration
Show Figures

Figure 1

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 Style

Bakare, 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

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop