{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T11:01:19Z","timestamp":1768734079534,"version":"3.49.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Friedreich\u2019s ataxia (FRDA), the most common recessive inherited ataxia, results from homozygous guanine\u2013adenine\u2013adenine (GAA) repeat expansions in intron 1 of the <jats:italic>FXN<\/jats:italic> gene, which leads to the deficiency of frataxin, a mitochondrial protein essential for iron-sulphur cluster synthesis. The study of frataxin protein regulation might yield new approaches for FRDA treatment. Here, we report tumorous imaginal disc 1 (TID1), a mitochondrial J-protein cochaperone, as a binding partner of frataxin that negatively controls frataxin protein levels. TID1 interacts with frataxin both <jats:italic>in vivo<\/jats:italic> in mouse cortex and <jats:italic>in vitro<\/jats:italic> in cortical neurons. Acute and subacute depletion of frataxin using RNA interference markedly increases TID1 protein levels in multiple cell types. In addition, TID1 overexpression significantly increases frataxin precursor but decreases intermediate and mature frataxin levels in HEK293 cells. In primary cultured human skin fibroblasts, overexpression of TID1S results in decreased levels of mature frataxin and increased fragmentation of mitochondria. This effect is mediated by the last 6 amino acids of TID1S as a peptide made from this sequence rescues frataxin deficiency and mitochondrial defects in FRDA patient-derived cells. Our findings show that TID1 negatively modulates frataxin levels, and thereby suggests a novel therapeutic target for treating FRDA.<\/jats:p>","DOI":"10.3389\/fphar.2024.1352311","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T04:52:40Z","timestamp":1709268760000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A peptide derived from TID1S rescues frataxin deficiency and mitochondrial defects in FRDA cellular models"],"prefix":"10.3389","volume":"15","author":[{"given":"Yi Na","family":"Dong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie Vanessa","family":"Ngaba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miniat W.","family":"Adeshina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Warren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johnathan","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1016\/j.ygeno.2006.06.015","article-title":"GAA repeat expansion mutation mouse models of Friedreich ataxia exhibit oxidative stress leading to progressive neuronal and cardiac pathology","volume":"88","author":"Al-Mahdawi","year":"2006","journal-title":"Genomics"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2520","DOI":"10.1158\/0008-5472.CAN-03-2735","article-title":"Tid-1 interacts with the von Hippel-Lindau protein and modulates angiogenesis by destabilization of HIF-1alpha","volume":"65","author":"Bae","year":"2005","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e223","DOI":"10.1212\/NXG.0000000000000223","article-title":"ACO2 homozygous missense mutation associated with complicated hereditary spastic paraplegia","volume":"4","author":"Bouwkamp","year":"2018","journal-title":"Neurol. 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