BackgroundRecent evidence has brought the mitochondrial contact sites, in communication with other organelles, to the centre of interest in cellular metabolism because of their essential role in many events surrounding the homeostasis of the human organism, including mitohormesis. Scope and approachThese mitochondrial dynamic structures are particularly active in response to feeding, after which the complex metabolic processes that produce energy from macronutrients in the mitochondria are also the largest producers of reactive oxygen species. However, little is known about the potential role of the rich lipid-binding protein coat of the outer mitochondrial membrane and the membrane of other organelles at mitochondrial contact sites as a place for transient storage and mobilisation of lipophilic antioxidant micronutrients, where they could function to promote mitohormesis. This commentary aims to assess the extent to which some of these lipid-binding proteins at mitochondrial contact sites are able to regulate the disposition of some lipophilic dietary antioxidants, such as β-carotene. Key findingsIt is found that the mitochondrial lipid-binding protein steroidogenic acute regulatory (StAR)-related lipid transfer (START) domain 1 (STARD1), the endoplasmic reticulum lipid-binding protein ASTER (with a StAR-like domain), and the endosomal lipid-binding proteins stabilins (with multiple fasciclin-1 adhesion domains) could work together at mitochondrial contact sites to allow the compartmentalisation and distribution of β-carotene and other dietary lipophilic antioxidants, which could help maintain the state of mitochondrial resistance to oxidative distress in the context of a healthy diet. ConclusionsThe surface of the outer mitochondrial membrane at contact sites during mitochondrial dynamics may have the potential to act as a functional platform for lipophilic antioxidant micronutrients that can eventually be mobilised to cope with supraphysiological levels of reactive oxygen species.