{
  "id": 10480530,
  "title": "Targeting ALCAT1 Ameliorates Cardiomyopathy in Barth Syndrome",
  "url": "https://urgent.news/2026/09/28/targeting-alcat1-ameliorates-cardiomyopathy-in-barth-syndrome",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-28T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754267v1?rss=1"
  },
  "original_language": "en",
  "account": "Barth syndrome is a X-linked mitochondrial disorder resulting from TAFAZZIN (TAZ) mutations, leading to cardiomyopathy and early demise. The connection between TAZ deficiency and impaired mitochondrial quality control is not fully understood, and no disease-modifying treatments exist for BTHS. Researchers examined the role of Acyl-CoA Lysocardiolipin Acyltransferase-1 (ALCAT1), a stress-inducible phospholipid-remodeling enzyme, in BTHS cardiomyopathy using TAZ knockdown and knockout mice. They assessed cardiac function, exercise capacity, mitochondrial function, lipid remodeling, lysosomal function, and mitophagic flux. ALCAT1 levels rose significantly in TAZ-deficient hearts. Deleting ALCAT1 or using the selective small molecule ALCAT1 inhibitor Juvenatin improved cardiac function in TAZKD mice and reversed existing cardiomyopathy in TAZcKO mice. ALCAT1 inhibition also enhanced mitochondrial structure, respiration, and reduced oxidative stress, without correcting the distinct cardiolipin abnormalities caused by TAZ deficiency. Instead, ALCAT1 deletion or inhibition rectified abnormal phosphatidylinositol/phosphoinositide signaling, restored lysosomal function, and improved mitophagy, resulting in better mitochondrial quality control in TAZ-deficient cells. Genetic and pharmacological targeting of ALCAT1 restores cardiac and mitochondrial function, even with persistent cardiolipin abnormalities, making ALCAT1 a promising disease-modifying therapeutic target for BTHS.",
  "summary": "Background: Barth syndrome (BTHS) is an X-linked mitochondrial disorder caused by loss-of-function mutations in TAFAZZIN (TAZ), resulting in defective cardiolipin (CL) remodeling, cardiomyopathy, and premature death. The mechanisms linking TAZ deficiency to impaired mitochondrial quality control remain incompletely understood, and there are no disease-modifying therapies available for BTHS. Here,…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}