Plants are our main food and feed source, but they often get threatened by adverse environments in which they must adapt to survive. These adverse environments due to (a)biotic factors cause major yield losses, that are expected to become worse due to climate change, raising the demand for stress tolerant crops. Mitochondria contain their own genome whose expression needs to be coordinated with the nuclear genome. This resulted in an extensive mitochondria-to-nucleus signalling network: ‘mitochondrial retrograde regulation’ (MRR). Plant mitochondria have a major function in energy production but altering mitochondrial function also has drastic effects on the plant’s resistance to various (a)biotic stresses, indicating that mitochondria play a crucial role in sensing and reporting stress signals to the nucleus. The host lab previously identified a novel MRR pathway mediated by NAC transcription factors (TF) that are stored at ER membranes. Upon mitochondrial perturbation by stresses, these TFs are released from the ER membranes and translocated to the nucleus, but the underlying molecular mechanisms of how mitochondria signal to activate these TFs in the ER are not understood. This project aims to identify the proteases responsible for NAC cleavage using state-of-the-art proteomics and chemical-biology approaches and thereby aims to expand our fragmentary understanding of how mitochondria communicate to other organelles and eventually the nucleus during plant stress responses.