Prohibitins comprise an evolutionarily conserved and ubiquitously expressed 
family of membrane proteins with poorly described functions. Large assemblies of 
PHB1 and PHB2 subunits are localized in the inner membrane of mitochondria, but 
various roles in other cellular compartments have also been proposed for both 
proteins. Here, we used conditional gene targeting of murine Phb2 to define 
cellular activities of prohibitins. Our experiments restrict the function of 
prohibitins to mitochondria and identify the processing of the dynamin-like 
GTPase OPA1, an essential component of the mitochondrial fusion machinery, as 
the central cellular process controlled by prohibitins. Deletion of Phb2 leads 
to the selective loss of long isoforms of OPA1. This results in an aberrant 
cristae morphogenesis and an impaired cellular proliferation and resistance 
toward apoptosis. Expression of a long OPA1 isoform in PHB2-deficient cells 
suppresses these defects, identifying impaired OPA1 processing as the primary 
cellular defect in the absence of prohibitins. Our results therefore assign an 
essential function for the formation of mitochondrial cristae to prohibitins and 
suggest a coupling of cell proliferation to mitochondrial morphogenesis.