{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T01:31:30Z","timestamp":1776216690641,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015826","name":"Korean Society of Ginseng","doi-asserted-by":"publisher","award":["2022"],"award-info":[{"award-number":["2022"]}],"id":[{"id":"10.13039\/501100015826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015826","name":"Korean Society of Ginseng","doi-asserted-by":"publisher","award":["2021R1F1A1062019"],"award-info":[{"award-number":["2021R1F1A1062019"]}],"id":[{"id":"10.13039\/501100015826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015826","name":"Korean Society of Ginseng","doi-asserted-by":"publisher","award":["2022R1A2C3005747"],"award-info":[{"award-number":["2022R1A2C3005747"]}],"id":[{"id":"10.13039\/501100015826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015826","name":"Korean Society of Ginseng","doi-asserted-by":"publisher","award":["2020R1A2C1004397"],"award-info":[{"award-number":["2020R1A2C1004397"]}],"id":[{"id":"10.13039\/501100015826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean Government (MSIP)","award":["2022"],"award-info":[{"award-number":["2022"]}]},{"name":"Korean Government (MSIP)","award":["2021R1F1A1062019"],"award-info":[{"award-number":["2021R1F1A1062019"]}]},{"name":"Korean Government (MSIP)","award":["2022R1A2C3005747"],"award-info":[{"award-number":["2022R1A2C3005747"]}]},{"name":"Korean Government (MSIP)","award":["2020R1A2C1004397"],"award-info":[{"award-number":["2020R1A2C1004397"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Astrocytes play a key role in brain functioning by providing energy to neurons. Increased astrocytic mitochondrial functions by Korean red ginseng extract (KRGE) have been investigated in previous studies. KRGE administration induces hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) and vascular endothelial growth factor (VEGF) in astrocytes in the adult mouse brain cortex. VEGF expression can be controlled by transcription factors, such as the HIF-1\u03b1 and estrogen-related receptor \u03b1 (ERR\u03b1). However, the expression of ERR\u03b1 is unchanged by KRGE in astrocytes of the mouse brain cortex. Instead, sirtuin 3 (SIRT3) expression is induced by KRGE in astrocytes. SIRT3 is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that resides in the mitochondria and maintains mitochondrial homeostasis. Mitochondrial maintenance requires oxygen, and active mitochondria enhance oxygen consumption, resulting in hypoxia. The effects of SIRT3 on HIF-1\u03b1-mediated mitochondria functions induced by KRGE are not well established. We aimed to investigate the relationship between SIRT3 and HIF-1\u03b1 in KRGE-treated normoxic astrocyte cells. Without changing the expression of the ERR\u03b1, small interfering ribonucleic acid targeted for SIRT3 in astrocytes substantially lowers the amount of KRGE-induced HIF-1\u03b1 proteins. Reduced proline hydroxylase 2 (PHD2) expression restores HIF-1\u03b1 protein levels in SIRT3-depleted astrocytes in normoxic cells treated with KRGE. The translocation of outer mitochondrial membranes 22 (Tom22) and Tom20 is controlled by the SIRT3-HIF-1\u03b1 axis, which is activated by KRGE. KRGE-induced Tom22 increased oxygen consumption and mitochondrial membrane potential, as well as HIF-1\u03b1 stability through PHD2. Taken together, in normoxic astrocytes, KRGE-induced SIRT3 activated the Tom22\u2013HIF-1\u03b1 circuit by increasing oxygen consumption in an ERR\u03b1-independent manner.<\/jats:p>","DOI":"10.3390\/cells12111512","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T02:01:15Z","timestamp":1685498475000},"page":"1512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Korean Red Ginseng-Induced SIRT3 Promotes the Tom22\u2013HIF-1\u03b1 Circuit in Normoxic Astrocytes"],"prefix":"10.3390","volume":"12","author":[{"given":"Hyungsu","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunhong","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dohyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"},{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-7768","authenticated-orcid":false,"given":"Young-Myeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0242-9612","authenticated-orcid":false,"given":"Yoon Kyung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1146\/annurev-vision-100419-114940","article-title":"Aging of the retina: Molecular and metabolic turbulences and potential interventions","volume":"7","author":"Campello","year":"2021","journal-title":"Annu. 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