PLoS BiologyPub Date : 2023-08-25eCollection Date: 2023-08-01DOI: 10.1371/journal.pbio.3002265
Delphine Franssen, Anne-Simone Parent
{"title":"Emulsifiers during gestation: The risks of ultra-processed food revealed in mice.","authors":"Delphine Franssen, Anne-Simone Parent","doi":"10.1371/journal.pbio.3002265","DOIUrl":"10.1371/journal.pbio.3002265","url":null,"abstract":"<p><p>Several dietary components disrupt the control of energy balance. A new study in PLOS Biology shows that, in mice, maternal consumption of emulsifiers induces a rewiring of the hypothalamic feeding circuits and causes neuropsychological impairment in the offspring.</p>","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002265"},"PeriodicalIF":9.8,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10456185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10104708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2023-08-24eCollection Date: 2023-08-01DOI: 10.1371/journal.pbio.3002257
Alejandro O Sodero, Valeria C Castagna, Setiembre D Elorza, Sara M Gonzalez-Rodulfo, María A Paulazo, Jimena A Ballestero, Mauricio G Martin, María Eugenia Gomez-Casati
{"title":"Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging.","authors":"Alejandro O Sodero, Valeria C Castagna, Setiembre D Elorza, Sara M Gonzalez-Rodulfo, María A Paulazo, Jimena A Ballestero, Mauricio G Martin, María Eugenia Gomez-Casati","doi":"10.1371/journal.pbio.3002257","DOIUrl":"10.1371/journal.pbio.3002257","url":null,"abstract":"<p><p>Cholesterol contributes to neuronal membrane integrity, supports membrane protein clustering and function, and facilitates proper signal transduction. Extensive evidence has shown that cholesterol imbalances in the central nervous system occur in aging and in the development of neurodegenerative diseases. In this work, we characterize cholesterol homeostasis in the inner ear of young and aged mice as a new unexplored possibility for the prevention and treatment of hearing loss. Our results show that cholesterol levels in the inner ear are reduced during aging, an effect that is associated with an increased expression of the cholesterol 24-hydroxylase (CYP46A1), the main enzyme responsible for cholesterol turnover in the brain. In addition, we show that pharmacological activation of CYP46A1 with the antiretroviral drug efavirenz reduces the cholesterol content in outer hair cells (OHCs), leading to a decrease in prestin immunolabeling and resulting in an increase in the distortion product otoacoustic emissions (DPOAEs) thresholds. Moreover, dietary supplementation with phytosterols, plant sterols with structure and function similar to cholesterol, was able to rescue the effect of efavirenz administration on the auditory function. Altogether, our findings point towards the importance of cholesterol homeostasis in the inner ear as an innovative therapeutic strategy in preventing and/or delaying hearing loss.</p>","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002257"},"PeriodicalIF":9.8,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10435010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2023-08-24eCollection Date: 2023-08-01DOI: 10.1371/journal.pbio.3002171
Maria Milà-Guasch, Sara Ramírez, Sergio R Llana, Júlia Fos-Domènech, Lea Maria Dropmann, Macarena Pozo, Elena Eyre, Alicia G Gómez-Valadés, Arnaud Obri, Roberta Haddad-Tóvolli, Marc Claret
{"title":"Maternal emulsifier consumption programs offspring metabolic and neuropsychological health in mice.","authors":"Maria Milà-Guasch, Sara Ramírez, Sergio R Llana, Júlia Fos-Domènech, Lea Maria Dropmann, Macarena Pozo, Elena Eyre, Alicia G Gómez-Valadés, Arnaud Obri, Roberta Haddad-Tóvolli, Marc Claret","doi":"10.1371/journal.pbio.3002171","DOIUrl":"10.1371/journal.pbio.3002171","url":null,"abstract":"<p><p>Modern lifestyle is associated with a major consumption of ultra-processed foods (UPF) due to their practicality and palatability. The ingestion of emulsifiers, a main additive in UPFs, has been related to gut inflammation, microbiota dysbiosis, adiposity, and obesity. Maternal unbalanced nutritional habits during embryonic and perinatal stages perturb offspring's long-term metabolic health, thus increasing obesity and associated comorbidity risk. However, whether maternal emulsifier consumption influences developmental programming in the offspring remains unknown. Here, we show that, in mice, maternal consumption of dietary emulsifiers (1% carboxymethyl cellulose (CMC) and 1% P80 in drinking water), during gestation and lactation, perturbs the development of hypothalamic energy balance regulation centers of the progeny, leads to metabolic impairments, cognition deficits, and induces anxiety-like traits in a sex-specific manner. Our findings support the notion that maternal consumption of emulsifiers, common additives of UPFs, causes mild metabolic and neuropsychological malprogramming in the progeny. Our data call for nutritional advice during gestation.</p>","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002171"},"PeriodicalIF":9.8,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10083010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2023-08-24eCollection Date: 2023-08-01DOI: 10.1371/journal.pbio.3002264
Gail L Patricelli
{"title":"Behavioral ecology: New technology enables a more holistic view of complex animal behavior.","authors":"Gail L Patricelli","doi":"10.1371/journal.pbio.3002264","DOIUrl":"10.1371/journal.pbio.3002264","url":null,"abstract":"<p><p>As any animal observer will tell you, behavior is complex. A more holistic view of this complexity is emerging as technological advances enable the study of spatiotemporal variability and expand the focus from single components to behavioral systems.</p>","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002264"},"PeriodicalIF":9.8,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10435015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2023-08-22eCollection Date: 2023-08-01DOI: 10.1371/journal.pbio.3002251
Frank E Rheindt, Patrice Bouchard, Richard L Pyle, Francisco Welter-Schultes, Erna Aescht, Shane T Ahyong, Alberto Ballerio, Thierry Bourgoin, Luis M P Ceríaco, Dmitry Dmitriev, Neal Evenhuis, Mark J Grygier, Mark S Harvey, Maurice Kottelat, Nikita Kluge, Frank-T Krell, Jun-Ichi Kojima, Sven O Kullander, Paulo Lucinda, Christopher H C Lyal, Cristina Luisa Scioscia, Daniel Whitmore, Douglas Yanega, Zhi-Qiang Zhang, Hong-Zhang Zhou, Thomas Pape
{"title":"Tightening the requirements for species diagnoses would help integrate DNA-based descriptions in taxonomic practice.","authors":"Frank E Rheindt, Patrice Bouchard, Richard L Pyle, Francisco Welter-Schultes, Erna Aescht, Shane T Ahyong, Alberto Ballerio, Thierry Bourgoin, Luis M P Ceríaco, Dmitry Dmitriev, Neal Evenhuis, Mark J Grygier, Mark S Harvey, Maurice Kottelat, Nikita Kluge, Frank-T Krell, Jun-Ichi Kojima, Sven O Kullander, Paulo Lucinda, Christopher H C Lyal, Cristina Luisa Scioscia, Daniel Whitmore, Douglas Yanega, Zhi-Qiang Zhang, Hong-Zhang Zhou, Thomas Pape","doi":"10.1371/journal.pbio.3002251","DOIUrl":"10.1371/journal.pbio.3002251","url":null,"abstract":"<p><p>Modern advances in DNA sequencing hold the promise of facilitating descriptions of new organisms at ever finer precision but have come with challenges as the major Codes of bionomenclature contain poorly defined requirements for species and subspecies diagnoses (henceforth, species diagnoses), which is particularly problematic for DNA-based taxonomy. We, the commissioners of the International Commission on Zoological Nomenclature, advocate a tightening of the definition of \"species diagnosis\" in future editions of Codes of bionomenclature, for example, through the introduction of requirements for specific information on the character states of differentiating traits in comparison with similar species. Such new provisions would enhance taxonomic standards and ensure that all diagnoses, including DNA-based ones, contain adequate taxonomic context. Our recommendations are intended to spur discussion among biologists, as broad community consensus is critical ahead of the implementation of new editions of the International Code of Zoological Nomenclature and other Codes of bionomenclature.</p>","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002251"},"PeriodicalIF":7.8,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2023-08-22eCollection Date: 2023-08-01DOI: 10.1371/journal.pbio.3002108
Thomas S Kraft, Edmond Seabright, Sarah Alami, Samuel M Jenness, Paul Hooper, Bret Beheim, Helen Davis, Daniel K Cummings, Daniel Eid Rodriguez, Maguin Gutierrez Cayuba, Emily Miner, Xavier de Lamballerie, Lucia Inchauste, Stéphane Priet, Benjamin C Trumble, Jonathan Stieglitz, Hillard Kaplan, Michael D Gurven
{"title":"Metapopulation dynamics of SARS-CoV-2 transmission in a small-scale Amazonian society.","authors":"Thomas S Kraft, Edmond Seabright, Sarah Alami, Samuel M Jenness, Paul Hooper, Bret Beheim, Helen Davis, Daniel K Cummings, Daniel Eid Rodriguez, Maguin Gutierrez Cayuba, Emily Miner, Xavier de Lamballerie, Lucia Inchauste, Stéphane Priet, Benjamin C Trumble, Jonathan Stieglitz, Hillard Kaplan, Michael D Gurven","doi":"10.1371/journal.pbio.3002108","DOIUrl":"10.1371/journal.pbio.3002108","url":null,"abstract":"<p><p>The severity of infectious disease outbreaks is governed by patterns of human contact, which vary by geography, social organization, mobility, access to technology and healthcare, economic development, and culture. Whereas globalized societies and urban centers exhibit characteristics that can heighten vulnerability to pandemics, small-scale subsistence societies occupying remote, rural areas may be buffered. Accordingly, voluntary collective isolation has been proposed as one strategy to mitigate the impacts of COVID-19 and other pandemics on small-scale Indigenous populations with minimal access to healthcare infrastructure. To assess the vulnerability of such populations and the viability of interventions such as voluntary collective isolation, we simulate and analyze the dynamics of SARS-CoV-2 infection among Amazonian forager-horticulturalists in Bolivia using a stochastic network metapopulation model parameterized with high-resolution empirical data on population structure, mobility, and contact networks. Our model suggests that relative isolation offers little protection at the population level (expected approximately 80% cumulative incidence), and more remote communities are not conferred protection via greater distance from outside sources of infection, due to common features of small-scale societies that promote rapid disease transmission such as high rates of travel and dense social networks. Neighborhood density, central household location in villages, and household size greatly increase the individual risk of infection. Simulated interventions further demonstrate that without implausibly high levels of centralized control, collective isolation is unlikely to be effective, especially if it is difficult to restrict visitation between communities as well as travel to outside areas. Finally, comparison of model results to empirical COVID-19 outcomes measured via seroassay suggest that our theoretical model is successful at predicting outbreak severity at both the population and community levels. Taken together, these findings suggest that the social organization and relative isolation from urban centers of many rural Indigenous communities offer little protection from pandemics and that standard control measures, including vaccination, are required to counteract effects of tight-knit social structures characteristic of small-scale populations.</p>","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002108"},"PeriodicalIF":7.8,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10129337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2023-08-21eCollection Date: 2023-08-01DOI: 10.1371/journal.pbio.3002218
Adam J Dobson, Susanne Voigt, Luisa Kumpitsch, Lucas Langer, Emmely Voigt, Rita Ibrahim, Damian K Dowling, Klaus Reinhardt
{"title":"Mitonuclear interactions shape both direct and parental effects of diet on fitness and involve a SNP in mitoribosomal 16s rRNA.","authors":"Adam J Dobson, Susanne Voigt, Luisa Kumpitsch, Lucas Langer, Emmely Voigt, Rita Ibrahim, Damian K Dowling, Klaus Reinhardt","doi":"10.1371/journal.pbio.3002218","DOIUrl":"10.1371/journal.pbio.3002218","url":null,"abstract":"<p><p>Nutrition is a primary determinant of health, but responses to nutrition vary with genotype. Epistasis between mitochondrial and nuclear genomes may cause some of this variation, but which mitochondrial loci and nutrients participate in complex gene-by-gene-by-diet interactions? Furthermore, it remains unknown whether mitonuclear epistasis is involved only in the immediate responses to changes in diet, or whether mitonuclear genotype might modulate sensitivity to variation in parental nutrition, to shape intergenerational fitness responses. Here, in Drosophila melanogaster, we show that mitonuclear epistasis shapes fitness responses to variation in dietary lipids and amino acids. We also show that mitonuclear genotype modulates the parental effect of dietary lipid and amino acid variation on offspring fitness. Effect sizes for the interactions between diet, mitogenotype, and nucleogenotype were equal to or greater than the main effect of diet for some traits, suggesting that dietary impacts cannot be understood without first accounting for these interactions. Associating phenotype to mtDNA variation in a subset of populations implicated a C/T polymorphism in mt:lrRNA, which encodes the 16S rRNA of the mitochondrial ribosome. This association suggests that directionally different responses to dietary changes can result from variants on mtDNA that do not change protein coding sequence, dependent on epistatic interactions with variation in the nuclear genome.</p>","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002218"},"PeriodicalIF":9.8,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10441796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10062532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2023-08-18eCollection Date: 2023-08-01DOI: 10.1371/journal.pbio.3002198
Karin Mitosch, Martin Beyß, Prasad Phapale, Bernhard Drotleff, Katharina Nöh, Theodore Alexandrov, Kiran R Patil, Athanasios Typas
{"title":"A pathogen-specific isotope tracing approach reveals metabolic activities and fluxes of intracellular Salmonella.","authors":"Karin Mitosch, Martin Beyß, Prasad Phapale, Bernhard Drotleff, Katharina Nöh, Theodore Alexandrov, Kiran R Patil, Athanasios Typas","doi":"10.1371/journal.pbio.3002198","DOIUrl":"10.1371/journal.pbio.3002198","url":null,"abstract":"<p><p>Pathogenic bacteria proliferating inside mammalian host cells need to rapidly adapt to the intracellular environment. How they achieve this and scavenge essential nutrients from the host has been an open question due to the difficulties in distinguishing between bacterial and host metabolites in situ. Here, we capitalized on the inability of mammalian cells to metabolize mannitol to develop a stable isotopic labeling approach to track Salmonella enterica metabolites during intracellular proliferation in host macrophage and epithelial cells. By measuring label incorporation into Salmonella metabolites with liquid chromatography-mass spectrometry (LC-MS), and combining it with metabolic modeling, we identify relevant carbon sources used by Salmonella, uncover routes of their metabolization, and quantify relative reaction rates in central carbon metabolism. Our results underline the importance of the Entner-Doudoroff pathway (EDP) and the phosphoenolpyruvate carboxylase for intracellularly proliferating Salmonella. More broadly, our metabolic labeling strategy opens novel avenues for understanding the metabolism of pathogens inside host cells.</p>","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002198"},"PeriodicalIF":9.8,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PLoS BiologyPub Date : 2023-08-18eCollection Date: 2023-08-01DOI: 10.1371/journal.pbio.3002252
Youjin Oh, Eun-Seon Yoo, Sang Hyeon Ju, Eunha Kim, Seulgi Lee, Seyun Kim, Kevin Wickman, Jong-Woo Sohn
{"title":"GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice.","authors":"Youjin Oh, Eun-Seon Yoo, Sang Hyeon Ju, Eunha Kim, Seulgi Lee, Seyun Kim, Kevin Wickman, Jong-Woo Sohn","doi":"10.1371/journal.pbio.3002252","DOIUrl":"10.1371/journal.pbio.3002252","url":null,"abstract":"<p><p>It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However, little is known about intrinsic molecules regulating NPY/AgRP neuronal excitability to affect long-term metabolic function. Here, we found that the G protein-gated inwardly rectifying K+ (GIRK) channels are key to stabilize NPY/AgRP neurons and that NPY/AgRP neuron-selective deletion of the GIRK2 subunit results in a persistently increased excitability of the NPY/AgRP neurons. Interestingly, increased body weight and adiposity observed in the NPY/AgRP neuron-selective GIRK2 knockout mice were due to decreased sympathetic activity and EE, while food intake remained unchanged. The conditional knockout mice also showed compromised adaptation to coldness. In summary, our study identified GIRK2 as a key determinant of NPY/AgRP neuronal excitability and driver of EE in physiological and stress conditions.</p>","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002252"},"PeriodicalIF":9.8,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10216561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission.","authors":"Jiajia He, Ke Liu, Yifan Wu, Chenhui Zhao, Shuaijie Yan, Jia-Hui Chen, Lizhu Hu, Dongmei Wang, Fan Zheng, Wenfan Wei, Chao Xu, Chengdong Huang, Xing Liu, Xuebiao Yao, Lijun Ding, Zhiyou Fang, Ai-Hui Tang, Chuanhai Fu","doi":"10.1371/journal.pbio.3002247","DOIUrl":"10.1371/journal.pbio.3002247","url":null,"abstract":"<p><p>Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report that the fission yeast AAA-ATPase Yta4, which is the homolog of budding yeast Msp1 responsible for clearing mistargeted tail-anchored (TA) proteins on mitochondria, plays a critical role in preventing excessive mitochondrial fission. The absence of Yta4 leads to mild mitochondrial fragmentation in a Dnm1-dependent manner but severe mitochondrial fragmentation upon induction of mitochondrial depolarization. Overexpression of Yta4 delocalizes the receptor proteins of Dnm1, i.e., Fis1 (a TA protein) and Mdv1 (the bridging protein between Fis1 and Dnm1), from mitochondria and reduces the localization of Dnm1 to mitochondria. The effect of Yta4 overexpression on Fis1 and Mdv1, but not Dnm1, depends on the ATPase and translocase activities of Yta4. Moreover, Yta4 interacts with Dnm1, Mdv1, and Fis1. In addition, Yta4 competes with Dnm1 for binding Mdv1 and decreases the affinity of Dnm1 for GTP and inhibits Dnm1 assembly in vitro. These findings suggest a model, in which Yta4 inhibits mitochondrial fission by inhibiting the function of the mitochondrial divisome composed of Fis1, Mdv1, and Dnm1. Therefore, the present work reveals an uncharacterized molecular mechanism underlying the inhibition of mitochondrial fission.</p>","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002247"},"PeriodicalIF":9.8,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}