|Mitochondrial dynamics caused by QoIs and SDHIs fungicides depended on FgDnm1 in Fusarium graminearum
|KANG Jin-bo, ZHANG Jie, LIU Yin-kai, SONG Ji-chang, OU Jian-lin, TAO Xian, ZHOU Ming-guo, DUAN Ya-bing
College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, P.R.China
禾谷镰刀菌（Fusarium graminearum）引起的小麦赤霉病（Fusarium head blight, FHB）是一种严重为害粮食作物的真菌病害，不仅引起作物产量损失与品质下降，而且病原菌在感病的谷粒中分泌的真菌毒素，严重威胁粮食安全。前期研究表明甲氧基丙烯酸酯类（quinone outside inhibitors, QoIs）和琥珀酸脱氢酶抑制剂类（succinate dehydrogenase inhibitors, SDHIs）杀菌剂可破坏线粒体动态平衡，引起线粒体碎片化。动力蛋白和动力相关蛋白（DRPs）作为GTPase超家族成员，参与调控真核细胞线粒体分裂、囊泡出芽与分裂等功能，但其在禾谷镰刀菌中的功能尚不清楚。在本研究中，我们利用BLAST分析发现禾谷镰孢菌中与酵母Dnm1的同源蛋白FgDnm1，并对其进行了生物学功能研究。结果表明，FgDnm1参与调控着菌丝生长、有性生殖及杀菌剂药敏性。此外，我们利用荧光标记技术和激光共聚焦显微镜发现FgDnm1与线粒体共定位，且参与调控禾谷镰刀菌产毒小体的结构形成及脱氧雪腐镰刀菌烯醇（DON）的生物合成。进一步研究表明，甲氧基丙烯酸酯类杀菌剂（QoIs）和琥珀酸脱氢酶抑制剂类杀菌剂（SDHIs）均会引起线粒体的碎片化，FgDnm1的缺失会导致线粒体呈现丝状网络分布，并阻断了QoIs和SDHIs诱导的线粒体碎片化。本研究揭示了线粒体动态平衡对禾谷镰刀菌菌丝生长发育、杀菌剂敏感性和毒素形成的影响。因此，我们推论QoIs与SDHIs杀菌剂引起的线粒体动态平衡变化依赖于FgDnm1。
Fusarium head blight (FHB) caused by Fusarium graminearum is a devastating fungal disease on small grain cereal crops, because it reduces yield and quality and causes the mycotoxin contamination to the grain. Dynamins and dynamin-related proteins (DRPs) are large GTPase superfamily members, which are typically involved in the budding and division of vesicles in eukaryotic cells, but their roles in Fusarium spp. remain unexplored. Here, we found that FgDnm1, a DRP and homolog to Dnm1 in Saccharomyces cerevisiae, contributes to the normal fungal growth, sexual reproduction and sensitivity to fungicides. In addition, we found FgDnm1 co-localizes with mitochondria and is involved in toxisome formation and deoxynivalenol (DON) production. Several quinone outside inhibitors (QoIs) and succinate dehydrogenase inhibitors (SDHIs) cause fragmentated morphology of mitochondria. Importantly, the deletion of FgDnm1 displays filamentous mitochondria and blocks the mitochondrial fragmentation induced by QoIs and SDHIs. Taken together, our studies uncover the effect of mitochondrial dynamics in fungal normal growth and how such events link to fungicides sensitivity and toxisome formation. Thus, we concluded that altered mitochondrial morphology induced by QoIs and SDHIs depends on FgDnm1.
Received: 18 January 2022
Accepted: 21 March 2022
This work was supported by the National Natural Science Foundation of China (31772190), the Jiangsu Agriculture Science and Technology Innovation Fund, China (JASTIF) (CX(21)2037), and the Postgraduate Research & Practice Innovation Program of Jiangsu Province, China (KYCX21_0631).
|About author: KANG Jin-bo, Tel: +86-25-84395249, E-mail: email@example.com; Correspondence DUAN Ya-bing, Tel: +86-25-84395641, E-mail: firstname.lastname@example.org
Cite this article:
KANG Jin-bo, ZHANG Jie, LIU Yin-kai, SONG Ji-chang, OU Jian-lin, TAO Xian, ZHOU Ming-guo, DUAN Ya-bing.
Mitochondrial dynamics caused by QoIs and SDHIs fungicides depended on FgDnm1 in Fusarium graminearum. Journal of Integrative Agriculture, 22(2): 481-494.
| Arakawa A, Kasai Y, Yamazaki K, Iwahashi F. 2018. Features of interactions responsible for antifungal activity against resistant type cytochrome bc1: A data-driven analysis based on the binding free energy at the atomic level. PLoS ONE, 13, e0207673.
Balaban R S, Nemoto S, Finkel T. 2005. Mitochondria, oxidants, and aging. Cell, 120, 483–495.
Bian C, Duan Y, Wang J, Xiu Q, Wang J, Hou Y, Song X, Zhou M. 2020. Validamycin a induces broad-spectrum resistance involving salicylic acid and jasmonic acid/Ethylene signaling pathways. Molecular Plant–Microbe Interactions, 33, 1424–1437.
Bleazard W, McCaffery J M, King E J, Bale S, Mozdy A, Tieu Q, Nunnari J, Shaw J M. 1999. The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nature Cell Biology, 1, 298–304.
Bossy-Wetzel E, Barsoum M J, Godzik A, Schwarzenbacher R, Lipton S A. 2003. Mitochondrial fission in apoptosis, neurodegeneration and aging. Current Opinion Cell Biology, 15, 706–716.
Casida J E, Durkin K A. 2017. Pesticide chemical research in toxicology: Lessons from nature. Chemical Research in Toxicology, 30, 94–104.
Champeil A, Doré T, Fourbet J F. 2004. Fusarium head blight: Epidemiological origin of the effects of cultural practices on head blight attacks and the production of mycotoxins by Fusarium in wheat grains. Plant Science, 166, 1389–1415.
Desbordes P, Essigmann B, Gary S, Gutbrod O, Maue M, Schwarz H G. 2020. Isoflucypram, the first representative of a new succinate dehydrogenase inhibitor fungicide subclass: Its chemical discovery and unusual binding mode. Pest Management Science, 76, 3340–3347.
Duan Y, Lu F, Zhou Z, Zhao H, Zhang J, Mao Y, Li M, Wang J, Zhou M. 2020. Quinone outside inhibitors affect DON biosynthesis, mitochondrial structure and toxisome formation in Fusarium graminearum. Jouranl of Hazardrous Materies, 398, 122908.
Fisher N, Meunier B, Biagini G A. 2020. The cytochrome bc1 complex as an antipathogenic target. FEBS Letters, 594, 2935–2952.
Gao S, Hu J. 2021. Mitochondrial fusion: The machineries in and out. Trends in Cell Biology, 31, 62–74.
Gisi U, Sierotzki H, Cook A, McCaffery A. 2002. Mechanisms influencing the evolution of resistance to Qo inhibitor fungicides. Pest Management Science, 58, 859–867.
Gomez-Suaga P, Paillusson S, Miller C C J. 2017a. ER-mitochondria signaling regulates autophagy. Autophagy, 13, 1250–1251.
Gomez-Suaga P, Paillusson S, Stoica R, Noble W, Hanger D P, Miller C C J. 2017b. The ER-mitochondria tethering complex VAPB-PTPIP51 regulates autophagy. Current Biology, 27, 371–385.
Griffin E E, Graumann J, Chan D C. 2005. The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria. Journal of Cell Biology, 170, 237–248.
Guillou E, Bousquet C, Daloyau M, Emorine L J, Belenguer P. 2005. Msp1p is an intermembrane space dynamin-related protein that mediates mitochondrial fusion in a Dnm1p-dependent manner in S. pombe. FEBS Letter, 579, 1109–1116.
Guo Q, Koirala S, Perkins E M, McCaffery J M, Shaw J M. 2012. The mitochondrial fission adaptors Caf4 and Mdv1 are not functionally equivalent. PLoS ONE, 7, e53523.
He L, Cui K, Song Y, Mu W, Liu F. 2018. High-efficiency control of gray mold by thenovel SDHI fungicide benzovindiflupyr combined with a reasonable application approach of dipping flower. Joural of Agricultural Food Chemistry, 66, 6692–6698.
Hirabayashi Y, Kwon S K, Paek H, Pernice W M, Paul M A, Lee J, Erfani P, Raczkowski A, Petrey D S, Pon L A, Polleux F. 2017. ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons. Science, 358, 623–630.
Huang X P, Luo J, Song Y F, Li B X, Mu W, Liu F. 2019. Favorable bioactivity of the SDHI fungicide benzovindiflupyr against Sclerotinia sclerotiorum mycelial growth, sclerotial production, and myceliogenic and carpogenic germination of sclerotia. Plant Disease, 103, 1613–1620.
Kamp H, Wahrheit J, Stinchcombe S, Walk T, Stauber F, Ravenzwaay B V. 2021. Succinate dehydrogenase inhibitors: In silico flux analysis and in vivo metabolomics investigations show no severe metabolic consequences for rats and humans. Food and Chemical Toxicology, 150, 112085.
Kennedy N W, Picton L K, Hill R B. 2020. Isolation and analysis of mitochondrial fission enzyme Dnm1 from Saccharomyces cerevisiae. Methods in Molecular Biology, 2159, 3–15.
Kou Y, He Y, Qiu J, Shu Y, Yang F, Deng Y. 2019. Mitochondrial dynamics and mitophagy are necessary for proper invasive growth in rice blast. Molecular Plant Pathology, 20, 1147–1162.
Lackner L L, Horner J S, Nunnari J. 2009. Mechanistic analysis of a dynamin effector. Science, 325, 874–877.
Liu S, Duan Y, Ge C, Chen C, Zhou M. 2013. Functional analysis of the β2-tubulin gene of Fusarium graminearum and the β-tubulin gene of Botrytis cinerea by homologous replacement. Pest Management Science, 69, 582–588.
Livak K J, Schmittgen T D. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔCT method. Methods, 25, 402–408.
Martinez-Guzman O, Willoughby M M, Saini A, Dietz J V, Bohovych I, Medlock A E. 2020. Mitochondrial-nuclear heme trafficking in budding yeast is regulated by GTPases that control mitochondrial dynamics and ER contact sites. Journal of Cell Science, 133, jcs237917.
Mears J A, Lackner L L, Fang S, Ingerman E, Nunnari J, Hinshaw J E. 2011. Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. Nature Structural & Molecular Biology, 18, 20–26.
Mozdy A D, McCaffery J M, Shaw J M. 2000. Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. Journal of Cell Biology, 151, 367–380.
Nagotu S, Krikken A M, Otzen M, Kiel J A, Veenhuis M, van der Klei I J. 2008. Peroxisome fission in Hansenula polymorpha requires Mdv1 and Fis1, two proteins also involved in mitochondrial fission. Traffic, 9, 1471–1484.
Navarro-Espíndola R, Takano-Rojas H, Suaste-Olmos F, Peraza-Reyes L. 2020. Distinct contributions of the peroxisome-mitochondria fission machinery during sexual development of the fungus Podospora anserina. Frontiers in Microbiology, 11, 640.
Pernas L, Scorrano L. 2016. Mito-morphosis: Mitochondrial fusion, fission, and cristae remodeling as key mediators of cellular function. Annual Review of Physiology, 78, 505–531.
Praefcke G J, McMahon H T. 2004. The dynamin superfamily: Universal membrane tubulation and fission molecules? Natural Review of Molecular Cell Biology, 5, 133–147.
Qin J, Wu M, Zhou S. 2020. FgEaf6 regulates virulence, asexual/sexual development and conidial septation in Fusarium graminearum. Current Genetics, 66, 517–529.
Qiu J B, Xu J H, Shi J R. 2014. Molecular characterization of the Fusarium graminearum species complex in eastern China. European Journal of Plant Pathology, 139, 811–823.
Ramachandran R, Schmid S L. 2018. The dynamin superfamily. Current Biology, 28, R411–R416.
Rapaport D, Brunner M, Neupert W, Westermann B. 1998. Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae. Journal of Biology Chemistry, 273, 20150–20155.
Raymond C K, Howald-Stevenson I, Vater C A, Stevens T H. 1992. Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants. Molecular Biology of the Cell, 3, 1389–1402.
Sesaki H, Jensen R E. 1999. Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape. Journal of Cell Biology, 147, 699–706.
Sesaki H, Jensen R E. 2001. UGO1 encodes an outer membrane protein required for mitochondrial fusion. Journal of Cell Biology, 152, 1123–1134.
Spier A, Stavru F, Cossart P. 2019. Interaction between intracellular bacterial pathogens and host cell mitochondria. Microbiology Spectrum, 7, 10.
Tanaka A, Cleland M M, Xu S, Narendra D P, Suen D F, Karbowski M, Youle R J. 2010. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. Journal of Cell Biology, 191, 1367–1380.
Tang G, Chen Y, Xu J R, Kistler H C, Ma Z. 2018. The fungal myosin I is essential for Fusarium toxisome formation. PLoS Pathogens, 14, e1006827.
Tieu Q, Nunnari J. 2000. Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division. Journal of Cell Biology, 151, 353–366.
Valente A J, Maddalena L A, Robb E L, Moradi F, Stuart J A. 2017. A simple ImageJ macro tool for analyzing mitochondrial network morphology in mammalian cell culture. Acta Histochemica, 119, 315–326.
Veeresh P, Kaur H, Sarmah D, Mounica L, Verma G, Kotian V, Kesharwani R, Kalia K, Borah A, Wang X, Dave K R, Rodriguez A, Yavagal D R, Bhattacharya P. 2019. Endoplasmic reticulum-mitochondria crosstalk: From junction to function across neurological disorders. Annals of the New York Academy of Sciences, 1457, 41–60.
Wang C F, Zhang S J, Hou R, Zhao Z T, Zheng Q, Xu Q J, Zheng D W, Wang G H, Liu H Q, Gao X L, Ma J W, Kistler H C, Kang Z S, Xu J R. 2011. Functional analysis of the kinome of the wheat scab fungus Fusarium graminearum. PLoS Pathogens, 7, e1002460
Xu C, Li M, Zhou Z, Li J, Chen D, Duan Y, Zhou M. 2019. Impact of five succinate dehydrogenase inhibitors on DON biosynthesis of Fusarium asiaticum, causing Fusarium head blight in wheat. Toxins, 11, 272.
Yang Y, Li M X, Duan Y B, Li T, Shi Y Y, Zhao D L. 2018. A new point mutation in β2-tubulin confers resistance to carbendazim in Fusarium asiaticum. Pesticide Biochemical Physiology, 145, 15–21.
Yoon Y, Krueger E W, Oswald B J, McNiven M A. 2003. The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Molecular Cell Biology, 23, 5409–5420.
Zhang Y, Chan D C. 2007. Structural basis for recruitment of mitochondrial fission complexes by Fis1. Proceedings of the National Academy of Sciences of the United States of America, 104, 18526–18530.
Zheng Z, Liu X, Li B, Cai Y, Zhu Y, Zhou M. 2016. Myosins FaMyo2B and Famyo2 affect asexual and sexual development, reduces pathogenicity, and FaMyo2B acts jointly with the myosin passenger protein fasmy1 to affect resistance to phenamacril in Fusarium asiaticum. PLoS ONE, 11, e0154058.
Zheng Z, Zhang Y, Wu X, Yang H, Ma L, Zhou M. 2018. FoMyo5 motor domain substitutions (Val151 to Ala and Ser418 to Thr) cause natural resistance to fungicide phenamacril in Fusarium oxysporum. Pesticide Biochemical Physiology, 147, 119–126.
Zhong K, Li X, Le X, Kong X, Zhang H, Zheng X. 2016. MoDnm1 dynamin mediating peroxisomal and mitochondrial fission in complex with MoFis1 and MoMdv1 is important for development of functional appressorium in Magnaporthe oryzae. PLoS Pathogens, 12, e1005823.
Zhou Z, Duan Y, Zhang J, Lu F, Zhu Y, Shim W B, Zhou M. 2021. Microtubule-assisted mechanism for toxisome assembly in Fusarium graminearum. Molecular Plant Pathology, 22, 163–174.
Zhou Z, Duan Y, Zhou M. 2020a. Carbendazim-resistance associated β2-tubulin substitutions increase deoxynivalenol biosynthesis by reducing the interaction between β2 -tubulin and IDH3 in Fusarium graminearum. Environmental Microbiology, 22, 598–614.
Zhou Z, Torres M, Sha H, Halbrook C J, Van den Bergh F, Reinert R B. 2020b. Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes. Science, 368, 54–60.
|No Suggested Reading articles found!