Liu 2020 Am J Physiol Heart Circ Physiol

From Bioblast
Publications in the MiPMap
Liu R, Jagannathan R, Sun L, Li F, Yang P, Lee J, Negi V, Perez-Garcia EM, Shiva S, Yechoor VK, Moulik M (2020) Tead1 is essential for mitochondrial function in cardiomyocytes. Am J Physiol Heart Circ Physiol 319:H89-99. https://doi.org/10.1152/ajpheart.00732.2019

Β» PMID: 32502376 Open Access

Liu Ruya, Jagannathan Rajaganapathi, Sun Lingfei, Li Feng, Yang Ping, Lee Jeongkyung, Negi Vinny, Perez-Garcia Eliana M, Shiva Sruti, Yechoor Vijay K, Moulik Mousumi (2020) Am J Physiol Heart Circ Physiol

Abstract: Mitochondrial dysfunction occurs in most forms of heart failure. We have previously reported that TEAD1, the transcriptional effector of Hippo pathway, is critical for maintaining adult cardiomyocyte function and its deletion in adult heart results in lethal acute dilated cardiomyopathy. Growing lines of evidence indicate that Hippo pathway plays a role in regulating mitochondrial function, though its role in cardiomyocytes is unknown. Here we show that TEAD1 plays a critical role in regulating mitochondrial OXPHOS in cardiomyocytes. Assessment of mitochondrial bioenergetics in isolated mitochondria from adult hearts showed that loss of Tead1 led to a significant decrease in respiratory rates, with both palmitoylcarnitine and pyruvate/malate substrates, and was associated with reduced electron transport chain complex I activity and expression. Transcriptomic analysis from Tead1-knockout myocardium revealed genes encoding oxidative phosphorylation, TCA cycle and fatty acid oxidation proteins as the top differentially enriched gene sets. Ex vivo loss-of-function of Tead1 in primary cardiomyocytes also showed diminished aerobic respiration and maximal mitochondrial oxygen consumption capacity, demonstrating that TEAD1 regulation of OXPHOS, in cardiomyocytes, is cell-autonomous. Taken together, our data demonstrate that TEAD1 is a crucial transcriptional node that is a cell-autonomous regulator a large network of mitochondrial function and biogenesis related genes essential for maintaining mitochondrial function and adult cardiomyocyte homeostasis. β€’ Keywords: Hippo pathway, TEAD1, Heart failure, Metabolism, Mitochondria β€’ Bioblast editor: Plangger M

Liu 2020 Am J Physiol Heart Circ Physiol CORRECTION.png

Correction: FADH2 and Complex II

Ambiguity alert.png
FADH2 is shown as the substrate feeding electrons into Complex II (CII). This is wrong and requires correction - for details see Gnaiger (2024).
Gnaiger E (2024) Complex II ambiguities ― FADH2 in the electron transfer system. J Biol Chem 300:105470. https://doi.org/10.1016/j.jbc.2023.105470 - Β»Bioblast linkΒ«

Hydrogen ion ambiguities in the electron transfer system

Communicated by Gnaiger E (2023-10-08) last update 2023-11-10
Electron (e-) transfer linked to hydrogen ion (hydron; H+) transfer is a fundamental concept in the field of bioenergetics, critical for understanding redox-coupled energy transformations.
Ambiguity alert H+.png
However, the current literature contains inconsistencies regarding H+ formation on the negative side of bioenergetic membranes, such as the matrix side of the mitochondrial inner membrane, when NADH is oxidized during oxidative phosphorylation (OXPHOS). Ambiguities arise when examining the oxidation of NADH by respiratory Complex I or succinate by Complex II.
Ambiguity alert e-.png
Oxidation of NADH or succinate involves a two-electron transfer of 2{H++e-} to FMN or FAD, respectively. Figures indicating a single electron e- transferred from NADH or succinate lack accuracy.
Ambiguity alert NAD.png
The oxidized NAD+ is distinguished from NAD indicating nicotinamide adenine dinucleotide independent of oxidation state.
NADH + H+ β†’ NAD+ +2{H++e-} is the oxidation half-reaction in this H+-linked electron transfer represented as 2{H++e-} (Gnaiger 2023). Putative H+ formation shown as NADH β†’ NAD+ + H+ conflicts with chemiosmotic coupling stoichiometries between H+ translocation across the coupling membrane and electron transfer to oxygen. Ensuring clarity in this complex field is imperative to tackle the apparent ambiguity crisis and prevent confusion, particularly in light of the increasing number of interdisciplinary publications on bioenergetics concerning diagnostic and clinical applications of OXPHOS analysis.


Labels: MiParea: Respiration, mtDNA;mt-genetics  Pathology: Cardiovascular 

Organism: Mouse  Tissue;cell: Heart  Preparation: Isolated mitochondria  Enzyme: Complex II;succinate dehydrogenase 

Coupling state: LEAK, OXPHOS  Pathway: F, N, NS  HRR: Oxygraph-2k 

2020-06 

Cookies help us deliver our services. By using our services, you agree to our use of cookies.