Epimedin C enhances mitochondrial energy supply by regulating the interaction between MIC25 and UBC in rodent model.

The study investigates the molecular mechanisms underlying the skeletal muscle-enhancing effects of Epimedin C, a natural flavonoid, focusing on its interaction with the mitochondrial cristae structural protein MIC25. Using C57BL/6 mice, we demonstrate that Epimedin C enhances exercise performance t...

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Main Authors: Mi Huang, Lei Yu, Zhong Li, Ying Wang, Chunlin Yang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0325031
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author Mi Huang
Lei Yu
Zhong Li
Ying Wang
Chunlin Yang
author_facet Mi Huang
Lei Yu
Zhong Li
Ying Wang
Chunlin Yang
author_sort Mi Huang
collection DOAJ
description The study investigates the molecular mechanisms underlying the skeletal muscle-enhancing effects of Epimedin C, a natural flavonoid, focusing on its interaction with the mitochondrial cristae structural protein MIC25. Using C57BL/6 mice, we demonstrate that Epimedin C enhances exercise performance through preservation of mitochondrial function. Proteomic analysis identified MIC25 as a key protein modulated by Epimedin C, whose stability is regulated via ubiquitin-dependent degradation. Functional experiments revealed that Epimedin C disrupts the interaction between MIC25 and ubiquitin-conjugating enzyme C (UBC), preventing MIC25 degradation and maintaining the integrity of the mitochondrial contact site and cristae organizing system (MICOS). This stabilization preserves mitochondrial cristae structure, improves ATP production, and delays muscle fatigue. Notably, MIC25 overexpression mimicked Epimedin C's effects, while its knockdown abolished these benefits. Our findings establish MIC25 as a critical effector of Epimedin C, elucidating a novel pathway through which flavonoids maintain mitochondrial homeostasis to enhance muscle function. These insights hold promise for developing therapies targeting muscle atrophy and metabolic disorders.
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institution Kabale University
issn 1932-6203
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publishDate 2025-01-01
publisher Public Library of Science (PLoS)
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spelling doaj-art-83e4d9e4b3274a5e91480b1da384bfd62025-08-20T03:47:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01205e032503110.1371/journal.pone.0325031Epimedin C enhances mitochondrial energy supply by regulating the interaction between MIC25 and UBC in rodent model.Mi HuangLei YuZhong LiYing WangChunlin YangThe study investigates the molecular mechanisms underlying the skeletal muscle-enhancing effects of Epimedin C, a natural flavonoid, focusing on its interaction with the mitochondrial cristae structural protein MIC25. Using C57BL/6 mice, we demonstrate that Epimedin C enhances exercise performance through preservation of mitochondrial function. Proteomic analysis identified MIC25 as a key protein modulated by Epimedin C, whose stability is regulated via ubiquitin-dependent degradation. Functional experiments revealed that Epimedin C disrupts the interaction between MIC25 and ubiquitin-conjugating enzyme C (UBC), preventing MIC25 degradation and maintaining the integrity of the mitochondrial contact site and cristae organizing system (MICOS). This stabilization preserves mitochondrial cristae structure, improves ATP production, and delays muscle fatigue. Notably, MIC25 overexpression mimicked Epimedin C's effects, while its knockdown abolished these benefits. Our findings establish MIC25 as a critical effector of Epimedin C, elucidating a novel pathway through which flavonoids maintain mitochondrial homeostasis to enhance muscle function. These insights hold promise for developing therapies targeting muscle atrophy and metabolic disorders.https://doi.org/10.1371/journal.pone.0325031
spellingShingle Mi Huang
Lei Yu
Zhong Li
Ying Wang
Chunlin Yang
Epimedin C enhances mitochondrial energy supply by regulating the interaction between MIC25 and UBC in rodent model.
PLoS ONE
title Epimedin C enhances mitochondrial energy supply by regulating the interaction between MIC25 and UBC in rodent model.
title_full Epimedin C enhances mitochondrial energy supply by regulating the interaction between MIC25 and UBC in rodent model.
title_fullStr Epimedin C enhances mitochondrial energy supply by regulating the interaction between MIC25 and UBC in rodent model.
title_full_unstemmed Epimedin C enhances mitochondrial energy supply by regulating the interaction between MIC25 and UBC in rodent model.
title_short Epimedin C enhances mitochondrial energy supply by regulating the interaction between MIC25 and UBC in rodent model.
title_sort epimedin c enhances mitochondrial energy supply by regulating the interaction between mic25 and ubc in rodent model
url https://doi.org/10.1371/journal.pone.0325031
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AT zhongli epimedincenhancesmitochondrialenergysupplybyregulatingtheinteractionbetweenmic25andubcinrodentmodel
AT yingwang epimedincenhancesmitochondrialenergysupplybyregulatingtheinteractionbetweenmic25andubcinrodentmodel
AT chunlinyang epimedincenhancesmitochondrialenergysupplybyregulatingtheinteractionbetweenmic25andubcinrodentmodel