Mito-nuclear incompatibility disrupts ACOX1/ACOX3-mediated mitochondria-peroxisome metabolic coordination in black soldier flies
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ID: 329383
2026
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Abstract
Mito-nuclear coadaptation is a fundamental evolutionary process linking genomic interactions to metabolic performance and organismal fitness. Although mito-nuclear incompatibility is known to impair mitochondrial function and contribute to hybrid breakdown, its effects on metabolic coordination between cellular organelles remain poorly understood, particularly in insects. Here, we used the black soldier fly (Hermetia illucens L.) as an experimental model and established a mito-nuclear incompatibility system by introducing heterologous mitochondrial genomes into a common nuclear background. Integrating genomic, transcriptomic, metabolomic, and functional analyses, we found that mito-nuclear mismatch disrupted not only mitochondrial oxidative phosphorylation but also peroxisome biogenesis and fatty acid metabolism. We identified the peroxisomal acyl-CoA oxidases ACOX1 and ACOX3 as important components associated with mito-nuclear incompatibility-induced disruption of mitochondria-peroxisome metabolic coordination. Functional knockdown of ACOX genes recapitulated major metabolic and fitness-related phenotypes associated with mito-nuclear mismatch, including energy deficiency, oxidative stress, delayed larval development, and reduced adult reproductive performance. Moreover, restoration of redox and energetic homeostasis partially rescued ACOX expression, whereas reinstating ACOX expression alleviated lipid metabolic defects in mismatched lines. Together, these findings support a model in which mito-nuclear incompatibility disrupts mitochondrial function and peroxisomal metabolic homeostasis, with reduced ACOX-dependent fatty acid metabolism representing an important component of broader mitochondria-peroxisome metabolic dysregulation. Our findings reveal a previously underappreciated role of mito-nuclear interactions in coordinating mitochondrial-peroxisomal metabolism and provide a mechanistic framework for understanding how genomic compatibility influences metabolic integration across cellular organelles.
| Reference Key |
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| Authors | Xue Wang, Shuyun Zhao, Guoxin Huang, Runjia Wang, Xinrui Ren, Jing Liu, Junkui Huang, Jinhua Xiao |
| Journal | molecular biology and evolution |
| Year | 2026 |
| DOI |
10.1093/molbev/msag241
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| URL | |
| Keywords | Keywords not found |
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