TY - JOUR T1 - PGC1α and Exercise Adaptations in Zebrafish JF - bioRxiv DO - 10.1101/483784 SP - 483784 AU - Alice Parisi AU - Peter Blattmann AU - Giulia Lizzo AU - Vivienne Stutz AU - Laura Strohm AU - Joy Richard AU - Gabriele Civiletto AU - Aline Charpagne AU - Frederic Raymond AU - Cedric Gobet AU - Benjamin Weger AU - Eugenia Migliavacca AU - Ruedi Aebersold AU - Bruce Spiegelman AU - Philipp Gut Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/12/07/483784.abstract N2 - Fish species display huge differences in physical activity ranging from lethargy to migration of thousands of miles, making them an interesting model to identify determinants of physical fitness. Here, we show a remarkable plasticity of zebrafish in response to exercise and induction of PGC1α (encoded by PPARGC1A), a dominant regulator of mitochondrial biogenesis. Forced expression of human PPARGC1A induces mitochondrial biogenesis, an exercise-like gene expression signature, and physical fitness comparable to wild-type animals trained in counter-current swim tunnels. Quantifying transcriptional and proteomic changes in response to exercise or PGC1α, we identify conserved ‘exercise’ adaptations, including a stoichiometric induction of the electron transport chain (ETC) that re-organizes into respiratory supercomplexes in both conditions. We further show that ndufa4/ndufa4l, previously assigned to complex I, associates to free and supramolecular complex IV in vivo. Thus, zebrafish is a useful and experimentally tractable vertebrate model to study exercise biology, including ETC expression and assembly.HIGHLIGHTSPGC1α reprograms zebrafish skeletal muscle to a ‘red fiber’ phenotype and increases exercise performanceZebrafish show a high molecular plasticity in response to PGC1α and exerciseSWATH-MS proteomics show a stoichiometric induction of the electron transport chain that organizes as supercomplexes in response to PGC1α and exercisendufa4/ndufa4l associate to free and supramolecular complex IV in vivo ER -