{
  "id": 2748433,
  "title": "Glycolytic compensation rather than NAD+/NADH balance sustains neuronal function during mitochondrial stress",
  "url": "https://urgent.news/2026/08/23/glycolytic-compensation-rather-than-nad-nadh-balance-sustains",
  "topic": "science",
  "section": "Science",
  "published": "2026-08-23T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.20.746069v1?rss=1"
  },
  "original_language": "en",
  "account": "When neurons face mitochondrial dysfunction, they activate compensatory pathways to ensure survival. In a previous study, researchers found that Drosophila neurons increase the transcription of lactate dehydrogenase (LDH) to help them survive the loss of a crucial mitochondrial fusion gene, Opa1. In this study, the researchers delve deeper into this metabolic flexibility and discover it is characterized by a general increase in glycolytic activity.\n\nAnother mitochondrial disturbance, the overexpression of TFAM, also triggers the expression of glycolytic genes, including LDH. Furthermore, this overexpression elevates lactate levels. LDH is essential for maintaining neuronal function under TFAM overexpression. Importantly, raising the NAD+/NADH ratio by expressing the bacterial NADH oxidase LbNOX does not replace the function of LDH. In fact, it exacerbates neuronal dysfunction in Opa1-deficient and TFAM-overexpressing neurons.\n\nMoreover, mitochondria-targeted LbNOX expression alone triggers mitochondrial dysfunction and activates the compensatory glycolytic response. In summary, these findings suggest that LDH-mediated rescue does not result from an increase in the NAD+/NADH ratio. Instead, it is part of a broader neuroprotective metabolic reprogramming that enables neurons to withstand various forms of mitochondrial impairment.",
  "summary": "Neurons engage compensatory pathways that promote survival when confronted with mitochondrial dysfunction. Indeed, we recently showed that Drosophila neurons upregulate Ldh transcription to help survive the loss of the key mitochondrial fusion gene Opa1. Here, we further characterize this metabolic flexibility and show that it reflects a more general increase in glycolytic activity. A distinct…",
  "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."
}