We are interested in understanding how a cell adapts its metabolic pathways in response to external stress and the model that we have focused on is the autophagy degradative pathway. During autophagy, membranes form from the endoplasmic reticulum and elongate to capture cytoplasmic targets including proteins or organelles such as mitochondria. The autophagy of mitochondria (aka mitophagy) is critical to maintain organelle quality control and overall metabolic fitness of the cell.
In recent years, we have investigated the regulatory mechanisms of autophagy, focusing on roles of the ATG1/ULK1 complex. Upon metabolic stress, such as amino acid starvation, the ULK1 complex becomes activated which signals downstream to the Beclin1-VPS34 phosphoinositide 3-kinase complex for the initiation of autophagy. Autophagosome membranes go on to capture cargo, which can be directed by a family of ubiquitin-binding adaptor proteins that recognise components specifically tagged for degradation, such as damaged mitochondria.