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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1434381

Hemichannels contribute to mitochondrial Ca 2+ and morphology alterations evoked by ethanol in astrocytes

Provisionally accepted
Tanhia F. Alvear Tanhia F. Alvear 1Arantza Farias-Pasten Arantza Farias-Pasten 1Sergio A. Vergara Sergio A. Vergara 1Juan Prieto-Villalobos Juan Prieto-Villalobos 1Antonia Silva-Contreras Antonia Silva-Contreras 1Fernando A. Fuenzalida Fernando A. Fuenzalida 1Rodrigo A. Quintanilla Rodrigo A. Quintanilla 2Juan A. Orellana Juan A. Orellana 1*
  • 1 Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
  • 2 Laboratory of Neurodegenerative Diseases, Instituto de Ciencias Biomédicas, Facultad de Ciencias de La Salud, Universidad Autónoma de Chile, Santiago, Chile

The final, formatted version of the article will be published soon.

    Alcohol, a toxic and psychoactive substance with addictive properties, severely impacts life quality, leading to significant health, societal, and economic consequences. Its rapid passage across the bloodbrain barrier directly affects different brain cells, including astrocytes. Our recent findings revealed the involvement of pannexin-1 (Panx1) and connexin-43 (Cx43) hemichannels in ethanol-induced dysfunction and astrocyte death. However, whether ethanol influences mitochondrial function and morphology in astrocytes, and the potential role of hemichannels in this process remains poorly understood. Ethanol reduced basal mitochondrial Ca 2+ but exacerbated thapsigargin-induced mitochondrial Ca 2+ dynamics in a concentration-dependent manner, as evidenced by Rhod-2 time-lapse recordings. Similarly, ethanol-treated astrocytes displayed increased mitochondrial superoxide production, as indicated by MitoSox labeling. These effects coincided with reduced mitochondrial membrane potential and increased mitochondrial fragmentation, as determined by MitoRed CMXRos and MitoGreen quantification, respectively. Crucially, inhibiting both Cx43 and Panx1 hemichannels effectively prevented all ethanol-induced mitochondrial abnormalities in astrocytes. We speculate that exacerbated hemichannel activity evoked by ethanol may impair intracellular Ca 2+ homeostasis, stressing mitochondrial Ca 2+ with potentially damaging consequences for mitochondrial fusion and fission dynamics and astroglial bioenergetics.

    Keywords: Mitochondria, astrocyte, Alcoholism, hemichannels, Connexin 43, Pannexin-1

    Received: 17 May 2024; Accepted: 03 Jul 2024.

    Copyright: © 2024 Alvear, Farias-Pasten, Vergara, Prieto-Villalobos, Silva-Contreras, Fuenzalida, Quintanilla and Orellana. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Juan A. Orellana, Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

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