{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:57:35Z","timestamp":1790377055286,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,24]],"date-time":"2023-12-24T00:00:00Z","timestamp":1703376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["NSTC 109-2314-B-002-121-MY3"],"award-info":[{"award-number":["NSTC 109-2314-B-002-121-MY3"]}]},{"name":"National Science and Technology Council","award":["NTUH 112-S257"],"award-info":[{"award-number":["NTUH 112-S257"]}]},{"DOI":"10.13039\/501100005762","name":"Executive Yuan, Taiwan and the National Taiwan University Hospital","doi-asserted-by":"publisher","award":["NSTC 109-2314-B-002-121-MY3"],"award-info":[{"award-number":["NSTC 109-2314-B-002-121-MY3"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005762","name":"Executive Yuan, Taiwan and the National Taiwan University Hospital","doi-asserted-by":"publisher","award":["NTUH 112-S257"],"award-info":[{"award-number":["NTUH 112-S257"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurofibromatosis type 1 (NF1) stands as a prevalent neurocutaneous disorder. Approximately a quarter of NF1 patients experience the development of plexiform neurofibromas, potentially progressing into malignant peripheral nerve sheath tumors (MPNST). FT895, an HDAC11 inhibitor, exhibits potent anti-tumor effects on MPNST cells and enhances the cytotoxicity of cordycepin against MPNST. The study aims to investigate the molecular mechanism underlying FT895\u2019s efficacy against MPNST cells. Initially, our study unveiled that FT895 disrupts mitochondrial biogenesis and function. Post-FT895 treatment, reactive oxygen species (ROS) in MPNST notably increased, while mitochondrial DNA copy numbers decreased significantly. Seahorse analysis indicated a considerable decrease in basal, maximal, and ATP-production-coupled respiration following FT895 treatment. Immunostaining highlighted FT895\u2019s role in promoting mitochondrial aggregation without triggering mitophagy, possibly due to reduced levels of XBP1, Parkin, and PINK1 proteins. Moreover, the study using CHIP-qPCR analysis revealed a significant reduction in the copy numbers of promoters of the MPV17L2, POLG, TFAM, PINK1, and Parkin genes. The RNA-seq analysis underscored the prominent role of the HIF-1\u03b1 signaling pathway post-FT895 treatment, aligning with the observed impairment in mitochondrial respiration. In summary, the study pioneers the revelation that FT895 induces mitochondrial respiratory damage in MPNST cells.<\/jats:p>","DOI":"10.3390\/ijms25010277","type":"journal-article","created":{"date-parts":[[2023,12,24]],"date-time":"2023-12-24T20:44:15Z","timestamp":1703450655000},"page":"277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["FT895 Impairs Mitochondrial Function in Malignant Peripheral Nerve Sheath Tumor Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Po-Yuan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neurology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10012, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-An","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10012, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Chih","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10012, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey-Ling","family":"You","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10012, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Jen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10012, Taiwan"},{"name":"Department of Medical Genetics, National Taiwan University Hospital, Taipei 10012, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/ng0296-144","article-title":"Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells","volume":"12","author":"Bollag","year":"1996","journal-title":"Nat. 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