tetano
Editor, Senior Moderator
iScience
. 2025 Mar 25;28(4):112291.
doi: 10.1016/j.isci.2025.112291. eCollection 2025 Apr 18. Somatic Miwi2 modulates mitochondrial function in airway multiciliated cells and exacerbates influenza pathogenesis
Jhonatan Henao Vasquez[SUP] 1 2 [/SUP], Jin Yuan[SUP] 1 [/SUP], Chi Jing Leow[SUP] 3 [/SUP], Erin Crossey[SUP] 1 [/SUP], Fengzhi Shao[SUP] 1 [/SUP], Senegal Carty[SUP] 1 2 [/SUP], Viviana A Dominguez[SUP] 2 [/SUP], Ming Lo[SUP] 4 5 [/SUP], Joseph P Mizgerd[SUP] 1 2 6 [/SUP], Jessica L Fetterman[SUP] 2 [/SUP], Nelson C Lau[SUP] 3 7 [/SUP], Alan Fine[SUP] 1 2 [/SUP], Matthew R Jones[SUP] 1 2 [/SUP]
Affiliations
MIWI2, a P element-induced wimpy testes (PIWI) argonaute protein known for suppressing retrotransposons during male gonadogenesis, has an unexplored role in mammalian somatic cells. We identify MIWI2 multiciliated (M2MC) cells as a rare subset of airway multiciliated cells and investigate MIWI2's function in antiviral host defense. We analyzed transcriptomes from Miwi2 heterozygous (Miwi2 [SUP]+/tom[/SUP]) and deficient (Miwi2 [SUP]tom/tom[/SUP]) mice following influenza A infection. During infection, Miwi2 deficiency was associated with reduced mitochondrial and ribosomal gene expression in M2MC cells, increased mitochondrial reactive oxygen species (ROS) production and ADP/ATP ratios in multiciliated cells, and enhanced viral clearance and recovery. Additionally, Miwi2-expressing cells exhibited reduced levels of small RNAs derived from nuclear mitochondrial DNA. These findings reveal a previously unrecognized role for Miwi2 in regulating small non-coding RNAs and mitochondrial oxidant production in somatic cells, indicating a function beyond its established germline activities. Our study identifies Miwi2/Piwil4 as a potential factor influencing susceptibility to severe respiratory infections.
Keywords: Biochemistry; Cell biology; Functional aspects of cell biology.
. 2025 Mar 25;28(4):112291.
doi: 10.1016/j.isci.2025.112291. eCollection 2025 Apr 18. Somatic Miwi2 modulates mitochondrial function in airway multiciliated cells and exacerbates influenza pathogenesis
Jhonatan Henao Vasquez[SUP] 1 2 [/SUP], Jin Yuan[SUP] 1 [/SUP], Chi Jing Leow[SUP] 3 [/SUP], Erin Crossey[SUP] 1 [/SUP], Fengzhi Shao[SUP] 1 [/SUP], Senegal Carty[SUP] 1 2 [/SUP], Viviana A Dominguez[SUP] 2 [/SUP], Ming Lo[SUP] 4 5 [/SUP], Joseph P Mizgerd[SUP] 1 2 6 [/SUP], Jessica L Fetterman[SUP] 2 [/SUP], Nelson C Lau[SUP] 3 7 [/SUP], Alan Fine[SUP] 1 2 [/SUP], Matthew R Jones[SUP] 1 2 [/SUP]
Affiliations
- PMID: 40241756
- PMCID: PMC12002665
- DOI: 10.1016/j.isci.2025.112291
MIWI2, a P element-induced wimpy testes (PIWI) argonaute protein known for suppressing retrotransposons during male gonadogenesis, has an unexplored role in mammalian somatic cells. We identify MIWI2 multiciliated (M2MC) cells as a rare subset of airway multiciliated cells and investigate MIWI2's function in antiviral host defense. We analyzed transcriptomes from Miwi2 heterozygous (Miwi2 [SUP]+/tom[/SUP]) and deficient (Miwi2 [SUP]tom/tom[/SUP]) mice following influenza A infection. During infection, Miwi2 deficiency was associated with reduced mitochondrial and ribosomal gene expression in M2MC cells, increased mitochondrial reactive oxygen species (ROS) production and ADP/ATP ratios in multiciliated cells, and enhanced viral clearance and recovery. Additionally, Miwi2-expressing cells exhibited reduced levels of small RNAs derived from nuclear mitochondrial DNA. These findings reveal a previously unrecognized role for Miwi2 in regulating small non-coding RNAs and mitochondrial oxidant production in somatic cells, indicating a function beyond its established germline activities. Our study identifies Miwi2/Piwil4 as a potential factor influencing susceptibility to severe respiratory infections.
Keywords: Biochemistry; Cell biology; Functional aspects of cell biology.