Building out the FBXL4-NIX-mitophagy axis

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Mitochondria are the power stations within nearly all human cells. From time to time these are decommisoned and new ones are made. The old or damaged mitochondria are delivered to the cell breakers yard or lysosome in a process called mitophagy. Mitophagy is important in developmental pathways but also in suppressing neurodegeneration and other pathophysological conditions. Sometimes mitophagy can be over-active and patients are left with too few mitochondria for the body's energy needs and suffer from mitochondrial depletion syndrome. This is the case for patients with a mutation in a gene called FBXL4. We have recently figured out how such mutations lead to this excess of mitophagy, by showing that FBXL4 controls the levels of another protein called NIX, which can dive into the mitochondria and effectively act as a notice of condemnation. Now we want to build on these findings and provide a more integrated view of the mitophagy process that looks at how the function of FBXL4 is choreographed with other proteins and modifications. Our work combines hypothesis-driven and more open-ended discovery based research which may lead to new ways of influencing mitochondrial health for the benefit of patients.