Emerging role of mitoNEET as mitochondrial sensor of hypoxia

Mitochondria are organelles whose function and dynamics, that is fission, fusion, transport and selective removal (mitophagy), are fundamental for eukaryotic cells. Their dysfunction is associated with age-related neurodegeneration and the aging immune system. MitoNEET, an iron-sulfur (Fe-S) cluster-containing protein localised at the outer membrane of mitochondria, has emerged as a key regulator of mitochondrial respiration and linked to fission, fusion, and mitophagy. In this perspective article, we discuss recent emerging evidence describing the mitoNEET [2Fe-2S] cluster role as a sensor of the cellular level of O2. These findings provide a mechanistic explanation of how mitochondria sense hypoxia, which affects their bioelectrochemistry and dynamics. We hope our data and analysis stimulate future research to fully understand the chemistry and biology of this intriguing Fe-S protein. These studies are expected to reveal new mechanistic insight into mitochondrial function and dynamics and help develop new therapeutics for inflammatory and age-related diseases.