Liu 2020 Am J Physiol Heart Circ Physiol

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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.

» PMID: 32502376

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.

Keywords: Hippo pathway, TEAD1, Heart failure, Metabolism, Mitochondria Bioblast editor: Plangger M


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

Organism: Mouse  Tissue;cell: Heart  Preparation: Isolated mitochondria 


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

2020-06