Iditarod, a Drosophila homolog of the Irisin precursor FNDC5, is critical for exercise performance and cardiac autophagy.
Proc Natl Acad Sci U S A
; 120(39): e2220556120, 2023 09 26.
Article
em En
| MEDLINE
| ID: mdl-37722048
ABSTRACT
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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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Fibronectinas
/
Proteínas de Drosophila
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2023
Tipo de documento:
Article