Activin Signaling Mediates Muscle-to-Adipose Communication in a Mitochondria Dysfunction-Associated Obesity Model

Abstract

Mitochondrial perturbation-associated dysregulation of one organ has been shown to nonautonomously affect the functions of other organs in both vertebrates and invertebrates. Using Drosophila as a genetic model organism, we characterized mitochondrial synchrony dysregulation across organs and uncovered that mitochondrial perturbation caused by complex I disruption in muscles remotely impairs mitochondrial function and lipid mobilization in the fat body, leading to obesity. We further identified that the TGF-β ligand Actβ, which is autonomously increased by muscular mitochondrial perturbation, mediates muscle-to-fat-body communication and synchronized mitochondrial dysregulation.