Sestrin regulates acute chill coma recovery in Drosophila melanogaster

Cobb, Tyler P.; Damschroder, Deena; Wessells, Robert J.

doi:10.1016/j.ibmb.2021.103548

Cited by 9 publications

(6 citation statements)

References 55 publications

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“…Idit was also important for resistance against various stresses, such as nutritional deprivation and cold exposure, and necessary for nutrition-dependent regulation of lifespan. Of note, both Idit and Sestrins, two exercise regulators in Drosophila , are both found to be required for cold resistance [( 55 ) and this study]. Both proteins are also involved in mammalian thermogenesis ( 5 , 56 , 57 ).…”

Section: Discussionmentioning

confidence: 82%

Iditarod , a Drosophila homolog of the Irisin precursor FNDC5 , is critical for exercise performance and cardiac autophagy

Cobb,

Hwang,

Soukar

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Mammalian FNDC5 encodes a protein precursor of Irisin, which is important for exercise-dependent regulation of whole-body metabolism. In a genetic screen in Drosophila , we identified Iditarod ( Idit ), which shows substantial protein homology to mouse and human FNDC5 , as a regulator of autophagy acting downstream of Atg1/Atg13. Physiologically, Idit -deficient flies showed reduced exercise performance and defective cold resistance, which were rescued by exogenous expression of Idit . Exercise training increased endurance in wild-type flies, but not in Idit -deficient flies. Conversely, Idit is induced upon exercise training, and transgenic expression of Idit in wild-type flies increased endurance to the level of exercise trained flies. Finally, Idit deficiency prevented both exercise-induced increase in cardiac Atg8 and exercise-induced cardiac stress resistance, suggesting that cardiac autophagy may be an additional mechanism by which Idit is involved in the adaptive response to exercise. Our work suggests an ancient role of an Iditarod/Irisin/FNDC5 family of proteins in autophagy, exercise physiology, and cold adaptation, conserved throughout metazoan species.

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Section: Discussionmentioning

confidence: 82%

Iditarod , a Drosophila homolog of the Irisin precursor FNDC5 , is critical for exercise performance and cardiac autophagy

Cobb,

Hwang,

Soukar

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…Increasing number of studies showed that sestrin played an important role in protecting organism against adverse stress. In Drosophila muscle and nervous system, sestrin was required for normal chill coma recovery after acute exposure to low temperatures (Cobb et al 2021). The Sestrin knock-out impaired the development and shortened the lifespan of Drosophila exposed to a low-leucine diet (Valenstein et al 2022).…”

Section: Discussionmentioning

confidence: 99%

Bletilla striata polysaccharides protect against mercury-induced oxidative damage to Drosophila midguts via modulation of sestrin

Chen

Wen

2022

Preprint

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Oxidative stress was one of the major causes of heavy metal-induced toxicity in organisms including Drosophila melanogaster. Bletilla striata polysaccharide (BSP) with anti-oxidative property has been recently recognized as a novel player in the management of oxidative stress response in organisms. Here, we took Drosophila midgut as a model to evaluate the protective effects of BSP (50 µg/mL) on mercury chloride-induced gastrointestinal adversities. As a result, BSP was found to significantly improve the survival rates and climbing ability of flies exposed to mercury. Further study demonstrated that BSP significantly alleviated the mercury-induced injury to midgut epithelium, at least partly, through increasing antioxidant enzyme activity (glutathione-S-transferase and superoxide dismutase), decreasing reactive oxidative species production, inhibiting cell apoptosis, restoring intestinal epithelial barrier and regulating stem cell-mediated tissue regeneration. Additionally, oxidative stress responsive gene sestrin was involved in the protection of BSP against mercury-induced oxidative damage to midguts. This study suggested that BSP has great potential for future application in the treatment and prevention of heavy metal-induced gastrointestinal adversities in mammals.

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“…In Drosophila, the single Sestrin ortholog is required for normal cold tolerance, as is PGC-1α. 6 Given that UCP1 is not known to act in insects, what is the downstream mechanism by which Sestrin/ PGC-1α protects against cold stress? One possibility is that increased autophagy and proteosomal activity are protective against cold, consistent with the observation that Antarctic insects upregulate Sestrin-dependent autophagy to protect against dehydration stress.…”

Section: E D I T O R I a L Sestrin/fndc5: An Ancient Axis Connecting ...mentioning

confidence: 99%

“…Adding further complexity to this question, Sestrin has also been associated with cold tolerance in insects. In Drosophila , the single Sestrin ortholog is required for normal cold tolerance, as is PGC‐1α 6 . Given that UCP1 is not known to act in insects, what is the downstream mechanism by which Sestrin/ PGC‐1α protects against cold stress?…”

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confidence: 99%