Harhous 2019 J Mol Cell Cardiol

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Harhous Z, Badawi S, Bona NG, Pillot B, Augeul L, Paillard M, Booz GW, Canet-Soulas E, Ovize M, Kurdi M, Bidaux G (2019) Critical appraisal of STAT3 pattern in adult cardiomyocytes. J Mol Cell Cardiol 131:91-100.

» PMID: 31022374

Harhous Z, Badawi S, Bona NG, Pillot B, Augeul L, Paillard M, Booz GW, Canet-Soulas E, Ovize M, Kurdi M, Bidaux G (2019) J Mol Cell Cardiol

Abstract: The signal transducer and activator of transcription 3, STAT3, transfers cellular signals from the plasma membrane to the nucleus, acting as a signaling molecule and a transcription factor. Reports proposed an additional non-canonical role of STAT3 that could regulate the activity of complexes I and II of the electron transport chain and the opening of the mitochondrial permeability transition pore (PTP) after ischemia-reperfusion in various cell types. The native expression of STAT3 in heart mitochondria, together with a direct versus an indirect transcriptional role in mitochondrial functions, have been recently questioned. The objective of the present study was to investigate the cellular distribution of STAT3 in mouse adult cardiomyocytes under basal and stress conditions, along with assessing its presence and activity in cardiac mitochondria using structural and functional approaches. The analysis of the spatial distribution of STAT3 signal in the cardiomyocytes interestingly showed that it is transversely distributed in along the T-tubules and in nucleus. This distribution was neither affected by hypoxia nor by hypoxia/re‑oxygenation conditions. Focusing on the mitochondrial STAT3 localization, our results suggest that serine-phosphorylated STAT3 (PS727-STAT3) and total STAT3 are detected in crude but not in pure mitochondria of mouse adult cardiomyocytes, under basal and ischemia-reperfusion conditions. The inhibition of STAT3, with a pre-validated non-toxic Stattic dose, had significant effects on mitochondrial respiration, but a weak effect on the calcium retention capacity. Overall, our results exclusively reveal a unique cellular distribution of STAT3 in mouse adult cardiomyocytes, along the T-tubules and in nucleus, under different conditions. They also challenge the expression and activity of STAT3 in mitochondria of these cells under basal conditions and following ischemia-reperfusion. In addition, our results underline technical methods, complemental to cell fractionation, to evaluate STAT3 roles during hypoxia-reoxygenation and at the interface between nucleus and endoplasmic reticulum.

Copyright © 2018. Published by Elsevier Ltd.

Keywords: Cardiomyocytes, Ischemia-reperfusion, Mitochondria, Mitochondria associated membranes, Subcellular distribution, T-tubules Bioblast editor: Plangger M O2k-Network Lab: FR Lyon Ovize M

Labels: MiParea: Respiration 

Stress:Ischemia-reperfusion  Organism: Mouse  Tissue;cell: Heart  Preparation: Isolated mitochondria 

Regulation: Calcium  Coupling state: OXPHOS, ET  Pathway: N, CIV, ROX  HRR: Oxygraph-2k 

Labels, 2019-04