{
  "id": 4683616,
  "title": "Mitochondrial genome instability disrupts brown adipose tissue through pseudohypoxia-iron-NAD⁺ axis",
  "url": "https://urgent.news/2026/08/31/mitochondrial-genome-instability-disrupts-brown-adipose-tissue",
  "topic": "science",
  "section": "Science",
  "published": "2026-08-31T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.28.747463v1?rss=1"
  },
  "original_language": "en",
  "account": "Brown adipose tissue (BAT) is a mitochondria-rich organ responsible for generating heat through high oxidative capacity. However, the impact of mitochondrial dysfunction on BAT function and metabolism is not fully understood. Researchers have utilized the Deletor mouse model to investigate the effects of progressive mtDNA deletion disease on BAT identity and metabolism.\n\nIn Deletor mice, BAT undergoes significant remodeling, characterized by structural damage, loss of thermogenic function, pseudohypoxic signaling, iron dysregulation, and NAD+/NADH redox imbalance. These changes result in a failure to produce heat when exposed to cold and an inability to switch to fatty acid oxidation. Metabolomic analysis revealed altered TCA cycle intermediates, a shift in glycolysis, and accumulation of specific amino acids.\n\nFurther investigation showed that inhibiting PHD, a protein involved in pseudohypoxia signaling, worsened the disease-associated features. Additionally, suppressing HIF-1, another factor in the pseudohypoxic pathway, attenuated the stress response. Nicotinamide riboside, a compound that boosts NAD+, alleviated the disease's metabolic and transcriptional abnormalities, restoring the NAD+/NADH balance, suppressing the ISRmt, iron-stress, and pseudohypoxic gene programs, and correcting irregularities in carnitine and acylcarnitine levels.\n\nThese findings suggest that the pseudohypoxia-iron-NAD+ axis plays a crucial role in BAT dysfunction in mitochondrial disease. By targeting this axis, it may be possible to develop therapeutic strategies to restore BAT function and improve the metabolic health of those affected by mitochondrial disorders.",
  "summary": "Brown adipose tissue (BAT) is a mitochondria-rich thermogenic organ whose function depends on high oxidative capacity, yet how primary mitochondrial dysfunction remodels BAT identity and metabolism remains poorly defined. Using the Deletor mouse model of progressive mtDNA deletion disease, we identify a pseudohypoxiairon-NAD+ axis as a central organiser of BAT pathology. Deletor BAT underwent…",
  "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."
}