The depletion of TFAM and p-β-catenin(S552) in mitochondria in response to BoAHV-1 productive infection leads to decreased mitochondrial biogenesis

IF 2.4 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology Pub Date : 2025-03-05 DOI:10.1016/j.vetmic.2025.110454

Jiayu Lin , Xiaotian Fu , Xuan Li , Xiuyan Ding , Shitao Li , Filomena Fiorito , Liqian Zhu

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引用次数: 0

Abstract

Varicellovirus bovinealpha (BoAHV) types 1(BoAHV-1) is one of the most significant viruses affecting cattle, causing substantial economic losses in the global cattle industry. Virus productive infection in cell cultures leads to mitochondrial dysfunction, resulting in the overproduction of reactive oxygen species (ROS), which act as inflammatory mediators and exert cytotoxic effects. But the underlying mechanisms remain poorly understood. Mitochondrial transcription factor A (TFAM) is a critical transcriptional activator of the mitochondrial DNA and plays a vital role in mitochondrial biogenesis. In this study, we report that virus acute infection in calves (at 4 days post-infection) increases TFAM protein expression and its accumulation in the peri-nuclear region in a subset of trigeminal ganglia (TG) neurons. Similarly, virus productive infection at later stages in MDBK cells also leads to increased TFAM protein expression and its accumulation in the nucleus. Using TFAM-specific siRNAs, we revealed that TFAM plays a significant role in BoAHV-1 productive infection. Consistent with decreased mitochondrial biogenesis, TFAM protein accumulation in mitochondria was significantly reduced following viral infection, which is corroborated by the reduced accumulation of TOM70 and Tim44 proteins in mitochondria. These proteins are key components of the mitochondrial membrane transport system that facilitates the translocation of TFAM into mitochondria. Interestingly, we found that a subset of β-catenin resides in mitochondria, and viral infection decreases the accumulation of transcriptionally active β-catenin, p-β-catenin(S552), in mitochondria. This may contribute to decreased mitochondrial biogenesis, as the β-catenin-specific inhibitor iCRT14 reduces the protein expression of Cytb, a key regulator of mitochondrial biosynthesis. Collectively, we suggest that the depletion of both TFAM and p-β-catenin(S552) in mitochondria may contribute to the mitochondrial dysfunction induced by BoAHV-1 productive infection.

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来源期刊

Veterinary microbiology 农林科学-兽医学

CiteScore

5.90

自引率

6.10%

发文量

221

审稿时长

52 days

期刊介绍： Veterinary Microbiology is concerned with microbial (bacterial, fungal, viral) diseases of domesticated vertebrate animals (livestock, companion animals, fur-bearing animals, game, poultry, fish) that supply food, other useful products or companionship. In addition, Microbial diseases of wild animals living in captivity, or as members of the feral fauna will also be considered if the infections are of interest because of their interrelation with humans (zoonoses) and/or domestic animals. Studies of antimicrobial resistance are also included, provided that the results represent a substantial advance in knowledge. Authors are strongly encouraged to read - prior to submission - the Editorials (''Scope or cope'' and ''Scope or cope II'') published previously in the journal. The Editors reserve the right to suggest submission to another journal for those papers which they feel would be more appropriate for consideration by that journal. Original research papers of high quality and novelty on aspects of control, host response, molecular biology, pathogenesis, prevention, and treatment of microbial diseases of animals are published. Papers dealing primarily with immunology, epidemiology, molecular biology and antiviral or microbial agents will only be considered if they demonstrate a clear impact on a disease. Papers focusing solely on diagnostic techniques (such as another PCR protocol or ELISA) will not be published - focus should be on a microorganism and not on a particular technique. Papers only reporting microbial sequences, transcriptomics data, or proteomics data will not be considered unless the results represent a substantial advance in knowledge. Drug trial papers will be considered if they have general application or significance. Papers on the identification of microorganisms will also be considered, but detailed taxonomic studies do not fall within the scope of the journal. Case reports will not be published, unless they have general application or contain novel aspects. Papers of geographically limited interest, which repeat what had been established elsewhere will not be considered. The readership of the journal is global.