PGC1a and Exercise Adaptations in Zebrafish

Abstract

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 PGC1 (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 PGC1, 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.\n\nHIGHLIGHTSO_LIPGC1 reprograms zebrafish skeletal muscle to a red fiber phenotype and increases exercise performance\nC_LIO_LIZebrafish show a high molecular plasticity in response to PGC1 and exercise\nC_LIO_LISWATH-MS proteomics show a stoichiometric induction of the electron transport chain that organizes as supercomplexes in response to PGC1 and exercise\nC_LIO_LIndufa4/ndufa4l associate to free and supramolecular complex IV in vivo\nC_LI