{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:20:24Z","timestamp":1789507224100,"version":"build-2803163510"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Drug resistance in fungal pathogens is a new challenge in clinical aspergillosis treatment. Mitochondria as dynamic organelles are involved in numerous biological processes in fungi, including drug resistance. However, little is known about the mechanism underlying mitochondrial regulation of the response of fungal pathogens to antifungal drugs. Here, we showed that a putative mitochondrial GTPase, GemA, a yeast Gem1 homolog, is crucial for the azole response and cell wall integrity in the opportunistic pathogen <jats:italic>Aspergillus fumigatus<\/jats:italic>. The fluorescence observation showed that GFP-labeled GemA is located in mitochondria, and loss of <jats:italic>gemA<\/jats:italic> results in aberrant giant mitochondrial morphology and abnormal mitochondrial membrane potential. Moreover, a \u0394<jats:italic>gemA<\/jats:italic> mutant attenuates fungal virulence in the <jats:italic>Galleria mellonella<\/jats:italic> model of aspergillosis. Furthermore, <jats:italic>gemA<\/jats:italic> loss increases resistance to azoles and terbinafine but not to amphotericin B. Of note, RNA-seq combined with RT-qPCR showed that a series of drug efflux pumps were upregulated in the <jats:italic>gemA<\/jats:italic> deletion mutant. Deleting <jats:italic>mdr1<\/jats:italic> or inhibiting the expression of drug efflux pumps can partially decrease the resistance to azoles resulting from the <jats:italic>gemA<\/jats:italic> mutant, implying that GemA influences azole response by affecting the expression of drug efflux pumps. Importantly, the \u0394<jats:italic>gemA<\/jats:italic> mutant is susceptible to the cell wall-perturbing reagent CR, but not to CFW, and this defect can be partly rescued by hyperosmotic stress. TEM revealed that the cell wall of \u0394<jats:italic>gemA<\/jats:italic> was thicker than that of the WT strain, demonstrating that GemA plays a role in cell wall composition and integrity. Collectively, we identified a putative mitochondrial GTPase, GemA, which is critical for hyphal growth, virulence, azole susceptibility, and cell wall integrity and acts by affecting mitochondrial function.<\/jats:p>","DOI":"10.3389\/fmicb.2022.957857","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T07:27:32Z","timestamp":1660030052000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Requirement of a putative mitochondrial GTPase, GemA, for azole susceptibility, virulence, and cell wall integrity in Aspergillus fumigatus"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaogang","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guorong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelian","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100940","DOI":"10.1016\/j.arr.2019.100940","article-title":"Mitochondria in the signaling pathways that control longevity and health span","volume":"54","author":"Akbari","year":"2019","journal-title":"Ageing Res. 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