Human Metapneumovirus Nucleoprotein Impairs Stress-Induced Mitophagy and Mitochondrial Quality Control
4 affiliations
- 1School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
- 2Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China
- 3School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China
- 4Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Abstract
Human metapneumovirus (HMPV) is an important respiratory pathogen for which specific antiviral therapies are currently unavailable, and the mechanisms by which HMPV regulates host mitochondrial homeostasis remain poorly understood. Here, we investigated the role of HMPV nucleoprotein (N) in mitophagy regulation and mitochondrial quality control, with a focus on its association with selective autophagy-related factors. Using recombinant protein purification, surface plasmon resonance, co-immunoprecipitation, confocal microscopy, mitochondrial-targeted mitophagy reporter analysis, and immunoblotting, we examined the interaction between HMPV N and host autophagy-associated factors and evaluated its effects on mitophagy. We demonstrated that HMPV N interacts with TAX1BP1 and LC3, two key components of the selective autophagy machinery. HMPV N signals were spatially associated with mitochondrial regions, and HMPV N expression increased the spatial association of TAX1BP1-positive structures with mitochondria, while reducing the spatial association of LC3-positive structures with TOM20-positive mitochondria under stress conditions. Consistently, HMPV N expression reduced CCCP-induced mitochondrial delivery to acidic compartments and attenuated TOM20 degradation, while exerting limited effects on basal mitochondrial turnover. These findings identify HMPV N as a viral regulator of stress-induced mitophagy and suggest that its interactions with selective autophagy-associated factors contribute to altered mitochondrial homeostasis during infection.
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BibTeX
@article{xie2026human,
title = {{Human Metapneumovirus Nucleoprotein Impairs Stress-Induced Mitophagy and Mitochondrial Quality Control}},
author = {Jiayi Xie and Tong Ji and Min Zhou and Lingli Zheng and Kexin Zhang and Qian Lan and Yilin Mai and Meng Xu and Zhengfei Qi and Qingshan Bill Fu},
journal = {Biomolecules},
year = {2026},
month = nov,
doi = {10.3390/biom16111588},
url = {https://www.mdpi.com/2218-273X/16/11/1588},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Human Metapneumovirus Nucleoprotein Impairs Stress-Induced Mitophagy and Mitochondrial Quality Control
AU - Jiayi Xie
AU - Tong Ji
AU - Min Zhou
AU - Lingli Zheng
AU - Kexin Zhang
AU - Qian Lan
AU - Yilin Mai
AU - Meng Xu
AU - Zhengfei Qi
AU - Qingshan Bill Fu
PY - 2026
DA - 2026/11/01
JO - Biomolecules
DO - 10.3390/biom16111588
UR - https://www.mdpi.com/2218-273X/16/11/1588
AB - Human metapneumovirus (HMPV) is an important respiratory pathogen for which specific antiviral therapies are currently unavailable, and the mechanisms by which HMPV regulates host mitochondrial homeostasis remain poorly understood. Here, we investigated the role of HMPV nucleoprotein (N) in mitophagy regulation and mitochondrial quality control, with a focus on its association with selective autophagy-related factors. Using recombinant protein purification, surface plasmon resonance, co-immunoprecipitation, confocal microscopy, mitochondrial-targeted mitophagy reporter analysis, and immunoblotting, we examined the interaction between HMPV N and host autophagy-associated factors and evaluated its effects on mitophagy. We demonstrated that HMPV N interacts with TAX1BP1 and LC3, two key components of the selective autophagy machinery. HMPV N signals were spatially associated with mitochondrial regions, and HMPV N expression increased the spatial association of TAX1BP1-positive structures with mitochondria, while reducing the spatial association of LC3-positive structures with TOM20-positive mitochondria under stress conditions. Consistently, HMPV N expression reduced CCCP-induced mitochondrial delivery to acidic compartments and attenuated TOM20 degradation, while exerting limited effects on basal mitochondrial turnover. These findings identify HMPV N as a viral regulator of stress-induced mitophagy and suggest that its interactions with selective autophagy-associated factors contribute to altered mitochondrial homeostasis during infection.
SN - 2218-273X
ER -