The open reading frame YAL048c affects the secretion of proteinase A inS. cerevisiae

Wolff, Anne Mette; Petersen, J.; Nilsson-Tillgren, Torsten; Din, Nanni

doi:10.1002/(sici)1097-0061(19990330)15:5<427::aid-yea362>3.0.co;2-5

Cited by 12 publications

(1 citation statement)

References 32 publications

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“…Miro GTPase Gem1, conserved from fungi to mammals, is anchored to the mitochondrial outer membrane by the transmembrane domain at its C-terminus (Wolff et al, 1999 ; Fransson et al, 2003 ; Frederick et al, 2004 ). The remaining part is floating in the cytosol and senses the changes in Ca 2+ concentration by its two EF-hand domains (Fransson et al, 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Requirement of a putative mitochondrial GTPase, GemA, for azole susceptibility, virulence, and cell wall integrity in Aspergillus fumigatus

Zhou

Yang

et al. 2022

Front. Microbiol.

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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 Aspergillus fumigatus. The fluorescence observation showed that GFP-labeled GemA is located in mitochondria, and loss of gemA results in aberrant giant mitochondrial morphology and abnormal mitochondrial membrane potential. Moreover, a ΔgemA mutant attenuates fungal virulence in the Galleria mellonella model of aspergillosis. Furthermore, gemA 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 gemA deletion mutant. Deleting mdr1 or inhibiting the expression of drug efflux pumps can partially decrease the resistance to azoles resulting from the gemA mutant, implying that GemA influences azole response by affecting the expression of drug efflux pumps. Importantly, the ΔgemA 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 ΔgemA 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.

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Section: Introductionmentioning

confidence: 99%

Requirement of a putative mitochondrial GTPase, GemA, for azole susceptibility, virulence, and cell wall integrity in Aspergillus fumigatus

Zhou

Yang

et al. 2022

Front. Microbiol.

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Studies of yeast Kluyveromyces lactis mutations conferring super‐secretion of recombinant proteins

Bartkeviciūte¹,

Sasnauskas²

2002

Yeast

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We have isolated mutants responsible for a super-secretion phenotype in Kluyveromyces lactis using the gene coding for a Bacillus amyloliquefaciens α-amylase as a marker for secretion. These mutations defined two groups, dominant and recessive. The recessive mutant strain, which secreted the heterologous protein in five-fold excess compared to the wild-type strain, was used for the cloning of genes, restraining the super-secreting phenotype. In screening for genes affecting supersecreting phenotype, we found that multiple copies of 10 different independently isolated DNA sequences suppressed the super-secreting phenotype. The first among the genes characterized, named KlSEL1 ('secretion lowering') showed homology to Saccharomyces cerevisiae ORF YML013w. The KlSEL1 gene is predicted to encode a polypeptide of 620 amino acid residues containing a putative transmembrane domain and UBX domain, characteristic for the ubiquitin-regulatory proteins. We demonstrated that the disruption of the SEL1 orthologues in K. lactis and S. cerevisiae conferred the super-secreting phenotype. SEL1 isolated from S. cerevisiae suppressed the super-secretion phenotype in K. lactis klsel1 strain, likewise homologous KlSEL1 . No other phenotypic features for strains lacking the SEL1 gene were noticed except for the S. cerevisiae mutant growth being notably slower than in a wt strain. No growth changes were observed in the K. lactis klsel1 mutant. The set of genes (suppressors of over-secreting phenotype) could be attractive for further analysis of gene functions, super-secreting mechanisms and construction of new strains. This collection could be useful for the expedient construction of reduced yeast genomes, optimized for heterologous protein secretion. The KlSEL1 gene has been assigned EMBL Accession No. AJ488285.

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Calcium regulation of mitochondria motility and morphology

Jeyaraju

Cisbani

Pellegrini

2009

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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In the Fifties, electron microscopy studies on neuronal cells showed that mitochondria typically cluster at synaptic terminals, thereby introducing the concept that proper mitochondria trafficking and partitioning inside the cell could provide functional support to the execution of key physiological processes. Today, the notion that a central event in the life of every eukaryotic cell is to configure, maintain, and reorganize the mitochondrial network at sites of high energy demand in response to environmental and cellular cues is well established, and the challenge ahead is to define the underlying molecular mechanisms and regulatory pathways. Recent pioneering studies have further contributed to place mitochondria at the center of the cell biology by showing that the machinery governing remodeling of mitochondria shape and structure regulates the functional output of the organelle as the powerhouse of the cell, the gateway to programmed cell death, and the platform for Ca(2+) signaling. Thus, a raising issue is to identify the cues integrating mitochondria trafficking and dynamics into cell physiology and metabolism. Given the versatile function of calcium as a second messenger and of the role of mitochondria as a major calcium store, evidences are emerging linking Ca(2+) transients to the modulation of mitochondrial activities. This review focuses on calcium as a switch controlling mitochondria motility and morphology in steady state, stressed, and pathological conditions.

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The open reading frame YAL048c affects the secretion of proteinase A inS. cerevisiae

Cited by 12 publications

References 32 publications

Requirement of a putative mitochondrial GTPase, GemA, for azole susceptibility, virulence, and cell wall integrity in Aspergillus fumigatus

Requirement of a putative mitochondrial GTPase, GemA, for azole susceptibility, virulence, and cell wall integrity in Aspergillus fumigatus

Studies of yeast Kluyveromyces lactis mutations conferring super‐secretion of recombinant proteins

Calcium regulation of mitochondria motility and morphology

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