Proteome-wide quantitative analysis of redox cysteine availability in the Drosophila melanogaster eye reveals oxidation of phototransduction machinery during blue light exposure and age

Stanhope, Sarah C.; Brandwine-Shemmer, Tal; Blum, Hannah R.; Doud, Emma H.; Jannasch, Amber; Mosley, Amber L.; Minke, Baruch; Weake, Vikki M.

doi:10.1016/j.redox.2023.102723

Cited by 3 publications

(1 citation statement)

References 107 publications

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“…Sample preparation, mass spectrometry analysis, bioinformatics, and data evaluation for quantitative proteomics experiments were performed in collaboration with the Indiana University Proteomics Center for Proteome Analysis at the Indiana University School of Medicine (IUSM) similarly to previously published protocols ( Kumar et al, 2022 ; Morris et al, 2022 ; Soundararajan et al, 2022 ; Stanhope et al, 2023 ).…”

Section: Methodsmentioning

confidence: 99%

Characterization of endoplasmic reticulum-associated degradation in the human fungal pathogen Candida albicans

Doss,

Moore,

Harman

et al. 2023

PeerJ

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Background Candida albicans is the most prevalent human fungal pathogen. In immunocompromised individuals, C. albicans can cause serious systemic disease, and patients infected with drug-resistant isolates have few treatment options. The ubiquitin-proteasome system has not been thoroughly characterized in C. albicans. Research from other organisms has shown ubiquitination is important for protein quality control and regulated protein degradation at the endoplasmic reticulum (ER) via ER-associated protein degradation (ERAD). Methods Here we perform the first characterization, to our knowledge, of ERAD in a human fungal pathogen. We generated functional knockouts of C. albicans genes encoding three proteins predicted to play roles in ERAD, the ubiquitin ligases Hrd1 and Doa10 and the ubiquitin-conjugating enzyme Ubc7. We assessed the fitness of each mutant in the presence of proteotoxic stress, and we used quantitative tandem mass tag mass spectrometry to characterize proteomic alterations in yeast lacking each gene. Results Consistent with a role in protein quality control, yeast lacking proteins thought to contribute to ERAD displayed hypersensitivity to proteotoxic stress. Furthermore, each mutant displayed distinct proteomic profiles, revealing potential physiological ERAD substrates, co-factors, and compensatory stress response factors. Among candidate ERAD substrates are enzymes contributing to ergosterol synthesis, a known therapeutic vulnerability of C. albicans. Together, our results provide the first description of ERAD function in C. albicans, and, to our knowledge, any pathogenic fungus.

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Section: Methodsmentioning

confidence: 99%

Characterization of endoplasmic reticulum-associated degradation in the human fungal pathogen Candida albicans

Doss,

Moore,

Harman

et al. 2023

PeerJ

Self Cite

View full text Add to dashboard Cite

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Systematic assessment of transcriptomic and metabolic reprogramming by blue light exposure coupled with aging

Huang,

Zhou,

Zhou

et al. 2023

PNAS Nexus

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The prevalent use of light-emitting diodes (LEDs) has caused revolutionary changes in modern life, but the potential hazards to health of blue light are poorly understood. N6-methyladenosine (m6A) is the most prevalent posttranscriptional modification in eukaryotes and can modulate diverse physiological processes by regulating mRNA fate. Here, to understand the effects and molecular mechanisms of daily low-intensity blue light exposure (BLE) and ascertain whether m6A methylation plays a role in BLE-induced phenotypes, we constructed a series of Drosophila models under different durations of daily low-intensity BLE and obtained multiomics profiles. Our results revealed that BLE could induce transcriptomic, m6A epitranscriptomic, and metabolomic reprogramming in Drosophila along with aging process. Importantly, the m6A methylation sites enriched in the 5′ untranslated regions (UTRs) of Drosophila transcripts showed strong age specificity and could be altered by BLE. We experimentally validated that aging-related gene Tor and circadian rhythm-related gene per were regulated by 5′ UTR-enriched m6A methylation. Overall, our study provides a systematic assessment of m6A RNA methylome reprogramming by BLE and aging in Drosophila model.

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Toxic blue light drives the gut microbiota-mediated lipid accumulation to build tolerance inDrosophila

Takada,

Ichinose,

Fuse

et al. 2024

Preprint

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Blue light (BL), abundant in sunlight, is highly toxic to many insect species when exposure is excessive. While the physiological mechanisms of BL toxicity are being revealed, the evolutionary responses remain less explored. In this study, using Drosophila melanogaster as a model system, we conducted laboratory selection for over 60 generations under excessive BL exposure. The selected line (SL) flies exhibited enhanced BL-tolerance, and also increased body weight and lipid accumulation. Interestingly, we found elongated midgut in the SL flies, and increased microbiota, which was dominated by Acetobacter persici. The BL-tolerance and the lipid accumulation were dependent on the increment of gut microbiota. Genomic analysis identified mutations in the Hippo signaling pathway linked to midgut elongation, while transcriptome analysis showed downregulation of Tachykinin (Tk), a key suppressor of intestinal lipogenesis. Genetically induced lipid accumulation through manipulation of Tk or related lipogenic genes was sufficient to confer BL-tolerance. Moreover, our findings indicate that parental BL irradiation, along with accumulated mutations from laboratory selection, played a crucial role in midgut elongation and increased bacterial abundance. These findings reveal evolutionary responses to excessive BL exposure that shape host traits to maximize the benefits provided by gut microbiota.

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Proteome-wide quantitative analysis of redox cysteine availability in the Drosophila melanogaster eye reveals oxidation of phototransduction machinery during blue light exposure and age

Cited by 3 publications

References 107 publications

Characterization of endoplasmic reticulum-associated degradation in the human fungal pathogen Candida albicans

Characterization of endoplasmic reticulum-associated degradation in the human fungal pathogen Candida albicans

Systematic assessment of transcriptomic and metabolic reprogramming by blue light exposure coupled with aging

Toxic blue light drives the gut microbiota-mediated lipid accumulation to build tolerance inDrosophila

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