Signaling by Folded gastrulation is modulated by mitochondrial fusion and fission

Abstract

Mitochondria are increasingly being identified as integrators and regulators of cell signaling pathways. Folded gastrulation (Fog) is a secreted signaling molecule best known for its role in regulating cell shape change at the ventral furrow during gastrulation in Drosophila. Fog is thought to signal, through a G-protein-coupled receptor, to effect downstream cytoskeletal changes necessary for cell shape change. However, the mechanisms regulating Fog signaling that lead to change in cell morphology are poorly understood. This study describes the identification of proteins involved in mitochondrial fusion and fission as regulators of Fog signaling. Pro-fission factors were found to function as enhancers of signaling, whereas pro-fusion factors were found to have the opposite effect. Consistent with this, activation of Fog signaling resulted in mitochondrial fragmentation, and inhibiting this process could attenuate Fog signaling. The findings presented here show that mitochondria, through regulation of fusion and fission, function as downstream effectors and modulators of Fog signaling and Fog-dependent cell shape change.