이준희 (University of Michigan Medical School) | 한빛사논문 > 한빛사

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University of Michigan Medical School

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Proc. Natl. Acad. Sci. USA, Sep 26 2023, 120 (39) | https://doi.org/10.1073/pnas.2220556120 Iditarod, a Drosophila homolog of the Irisin precursor FNDC5, is critical for exercise performance and cardiac autophagy

Tyler Cobb ¹, Irene Hwang ², Michael Soukar ², Sim Namkoong ^{2 3}, Uhn-Soo Cho ⁴, Maryam Safdar ¹, Myungjin Kim ^{2 *}, Robert J Wessells ^{1 *}, Jun Hee Lee ^{2 *}

¹Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201.
²Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109.
³Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
⁴Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109.

^*Corresponding author: correspondence to Myungjin Kim, Robert J Wessells or Jun Hee Lee

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.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-09-20)
연구진국내+국외 연구진
분야 생명과학 > 생리학

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