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Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury

Carbon monoxide (CO) can confer protection against cellular stress, whereas the potential involvement of autophagy and lysosomal biogenesis remains incompletely understood. We demonstrate here that the activation of protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (PERK) with CO increas...

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Autores principales: Kim, Hyo Jeong, Joe, Yeonsoo, Rah, So-Young, Kim, Seul-Ki, Park, Se-Ung, Park, Jeongmin, Kim, Jin, Ryu, Jinhyun, Cho, Gyeong Jae, Surh, Young-Joon, Ryter, Stefan W., Kim, Uh-Hyun, Chung, Hun Taeg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193007/
https://www.ncbi.nlm.nih.gov/pubmed/30333475
http://dx.doi.org/10.1038/s41419-018-1112-x
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author Kim, Hyo Jeong
Joe, Yeonsoo
Rah, So-Young
Kim, Seul-Ki
Park, Se-Ung
Park, Jeongmin
Kim, Jin
Ryu, Jinhyun
Cho, Gyeong Jae
Surh, Young-Joon
Ryter, Stefan W.
Kim, Uh-Hyun
Chung, Hun Taeg
author_facet Kim, Hyo Jeong
Joe, Yeonsoo
Rah, So-Young
Kim, Seul-Ki
Park, Se-Ung
Park, Jeongmin
Kim, Jin
Ryu, Jinhyun
Cho, Gyeong Jae
Surh, Young-Joon
Ryter, Stefan W.
Kim, Uh-Hyun
Chung, Hun Taeg
author_sort Kim, Hyo Jeong
collection PubMed
description Carbon monoxide (CO) can confer protection against cellular stress, whereas the potential involvement of autophagy and lysosomal biogenesis remains incompletely understood. We demonstrate here that the activation of protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (PERK) with CO increased the nuclear translocation of transcription factor EB (TFEB). PERK activation by CO increased intracellular Ca(2+) concentration and the phosphatase activity of calcineurin against TFEB. Moreover, we found that in the deficiency of TFEB, CO not only failed to recruit Parkin to the mitochondria but also failed to increase expression of lysosomal genes such as Lamp1, CathB, and TPP1. Therefore, we suggest that CO increases mitophagy through TFEB nuclear translocation by PERK-calcinuerin activation. In addition, the inhibition of TFEB with siRNA against TFEB abrogated the increase of mtDNA with CO, markers of mitochondrial biogenesis such as PGC1α, NRF1, and TFAM, and the mitochondrial proteins COX II, COX IV, and cytochrome c. To investigate the effects of CO on mitochondrial homeostasis in vivo, mice were treated with lipopolysaccharide (LPS)/d-galactosamine (D-GalN). CO inhalation reduced liver injury after challenge with LPS/GalN. Furthermore, CO inhalation increased TFEB activation, mitophagy and mitochondrial biogenesis in mice treated with LPS/GalN. Our findings describe novel mechanisms underlying CO-dependent cytoprotection in hepatocytes and liver tissue via activation of TFEB-dependent mitophagy and associated induction of both lysosomal and mitochondrial biogenesis.
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spelling pubmed-61930072018-10-19 Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury Kim, Hyo Jeong Joe, Yeonsoo Rah, So-Young Kim, Seul-Ki Park, Se-Ung Park, Jeongmin Kim, Jin Ryu, Jinhyun Cho, Gyeong Jae Surh, Young-Joon Ryter, Stefan W. Kim, Uh-Hyun Chung, Hun Taeg Cell Death Dis Article Carbon monoxide (CO) can confer protection against cellular stress, whereas the potential involvement of autophagy and lysosomal biogenesis remains incompletely understood. We demonstrate here that the activation of protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (PERK) with CO increased the nuclear translocation of transcription factor EB (TFEB). PERK activation by CO increased intracellular Ca(2+) concentration and the phosphatase activity of calcineurin against TFEB. Moreover, we found that in the deficiency of TFEB, CO not only failed to recruit Parkin to the mitochondria but also failed to increase expression of lysosomal genes such as Lamp1, CathB, and TPP1. Therefore, we suggest that CO increases mitophagy through TFEB nuclear translocation by PERK-calcinuerin activation. In addition, the inhibition of TFEB with siRNA against TFEB abrogated the increase of mtDNA with CO, markers of mitochondrial biogenesis such as PGC1α, NRF1, and TFAM, and the mitochondrial proteins COX II, COX IV, and cytochrome c. To investigate the effects of CO on mitochondrial homeostasis in vivo, mice were treated with lipopolysaccharide (LPS)/d-galactosamine (D-GalN). CO inhalation reduced liver injury after challenge with LPS/GalN. Furthermore, CO inhalation increased TFEB activation, mitophagy and mitochondrial biogenesis in mice treated with LPS/GalN. Our findings describe novel mechanisms underlying CO-dependent cytoprotection in hepatocytes and liver tissue via activation of TFEB-dependent mitophagy and associated induction of both lysosomal and mitochondrial biogenesis. Nature Publishing Group UK 2018-10-17 /pmc/articles/PMC6193007/ /pubmed/30333475 http://dx.doi.org/10.1038/s41419-018-1112-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Hyo Jeong
Joe, Yeonsoo
Rah, So-Young
Kim, Seul-Ki
Park, Se-Ung
Park, Jeongmin
Kim, Jin
Ryu, Jinhyun
Cho, Gyeong Jae
Surh, Young-Joon
Ryter, Stefan W.
Kim, Uh-Hyun
Chung, Hun Taeg
Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury
title Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury
title_full Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury
title_fullStr Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury
title_full_unstemmed Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury
title_short Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury
title_sort carbon monoxide-induced tfeb nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193007/
https://www.ncbi.nlm.nih.gov/pubmed/30333475
http://dx.doi.org/10.1038/s41419-018-1112-x
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