Prohibitin function within mitochondria: Essential roles for cell proliferation and cristae morphogenesis

Prohibitins comprise an evolutionary conserved and ubiquitously expressed family of membrane proteins. Various roles in different cellular compartments have been proposed for prohibitin proteins. Recent experiments, however, identify large assemblies of two homologous prohibitin subunits, PHB1 and PHB2, in the inner membrane of mitochondria as the physiologically active structure. Mitochondrial prohibitin complexes control cell proliferation, cristae morphogenesis and the functional integrity of mitochondria. The processing of the dynamin-like GTPase OPA1, a core component of the mitochondrial fusion machinery, has been defined as a key process affected by prohibitins. The molecular mechanism of prohibitin function, however, remained elusive. The ring-like assembly of prohibitins and their sequence similarity with lipid raft-associated SPFH-family members suggests a scaffolding function of prohibitins, which may lead to functional compartmentalization in the inner membrane of mitochondria.