PHB2 connects mitochondrial membrane remodeling to selective autophagy

PHB2 (prohibitin 2), a well-known inner mitochondrial membrane mitophagy receptor, has recently emerged as a potential sensor of intracellular bacteria. A recent study shows that increased exposure of the inner mitochondrial membrane protein PHB2 enables its interaction with bacterial surface proteins and the recruitment of the E3 ubiquitin ligases ARIH1 (ariadne RBR E3 ubiquitin protein ligase 1) or PRKN (parkin RBR E3 ubiquitin protein ligase), thereby promoting xenophagy. This finding expands the role of damaged mitochondria from autophagic cargo to an active platform for antibacterial defense. It also raises broader questions regarding how an inner mitochondrial membrane protein becomes accessible to invading bacteria, why PHB2 can recognize bacterial proteins, and what determines whether exposed PHB2 promotes mitophagy, xenophagy, or co-degradation of both cargos. Here, we discuss PHB2 as a potential damage-unmasked bacterial sensor, the contribution of mitochondrial membrane remodeling to its exposure, and the evolutionary relationship between mitochondrial and bacterial recognition. We further consider whether impaired mitophagy may compromise xenophagic competence in aging and disease.