Mitochondria-Derived H₂O₂ Promotes Symmetry Breaking of the C. elegans Zygote

Symmetry breaking is an essential step in cell differentiation and early embryonic development. However, the molecular cues that trigger symmetry breaking remain largely unknown. Here, we show that mitochondrial H₂O₂ acts as a symmetry-breaking cue in the C. elegans zygote. We find that symmetry breaking is marked by a local H₂O₂ increase and coincides with a relocation of mitochondria to the cell cortex. Lowering endogenous H₂O₂ levels delays the onset of symmetry breaking, while artificially targeting mitochondria to the cellular cortex using a light-induced heterodimerization technique is sufficient to initiate symmetry breaking in a H₂O₂-dependent manner. In wild-type development, both sperm and maternal mitochondria contribute to symmetry breaking. Our findings reveal that mitochondrial H₂O₂-signaling promotes the onset of polarization, a fundamental process in development and cell differentiation, and this is achieved by both mitochondrial redistribution and differential H₂O₂-production.