ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Agnuside Stabilizes the Complex I Assembly Factor NDUFAF6 to Reinforce Mitochondrial Efficiency and Thermogenic Responsiveness.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- Natural Small Molecules Targeting Mitochondrial Quality Control for the Treatment of Metabolic Diseases: Mechanisms, Novel Formulations, and Translational Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
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Authors and funding
8 authors.
Funding
Abstract
Brown and beige adipocytes dissipate energy as heat, yet effective strategies to enhance their mitochondrial efficiency remain limited. Here, we identify Agnuside (AGN) as a selective stabilizer of the complex I assembly factor NDUFAF6. AGN directly binds cytosolic NDUFAF6, suppresses its ubiquitination, prolongs its half-life, and facilitates mitochondrial import, thereby reinforcing complex I assembly and promoting coordinated stabilization of complexes III and IV within the respirasome, without altering complex II, complex V, or global mitochondrial biogenesis. Functionally, AGN exhibits a demand-dependent metabolic profile. Under basal conditions, AGN enhances mitochondrial oxidative efficiency without activating overt UCP1-dependent uncoupling. In contrast, cold exposure or chronic high-fat feeding markedly potentiates its thermogenic impact, as evidenced by improved mitochondrial ultrastructure, increased UCP1 abundance, and elevated energy expenditure in brown adipose tissue, with similar mitochondrial reinforcement observed in inguinal white adipose tissue under sustained metabolic stress. Importantly, thermoneutral Ucp1 knockdown does not abolish AGN-mediated enhancement of respiratory complex assembly and ATP production, whereas genetic ablation of Ndufaf6 eliminates these effects. Together, these findings establish AGN-NDUFAF6 stabilization as a key regulatory mechanism governing adipose mitochondrial efficiency and thermogenic responsiveness, and highlight assembly-factor targeting as a promising strategy to restore oxidative metabolism in metabolic dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.