Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are proteins that are ubiquitously expressed, and are present in the nucleus, cytosol, and mitochondria. Depending on the cellular localization, PHB1 and PHB2 have distinctive functions, but more evidence suggests a critical role within mitochondria. In fact, PHB proteins are highly expressed in cells that heavily depend on mitochondrial function. In mitochondria, these two proteins assemble at the inner membrane to form a supra-macromolecular structure, which works as a scaffold for proteins and lipids regulating mitochondrial metabolism, including bioenergetics, biogenesis, and dynamics in order to determine the cell fate, death, or life. PHB alterations have been found in aging and cancer, as well as neurodegenerative, cardiac, and kidney diseases, in which significant mitochondrial impairments have been observed. The molecular mechanisms by which prohibitins regulate mitochondrial function and their role in pathology are reviewed and discussed herein.

The cAMP response element‐binding protein (CREB) is a ubiquitous transcription factor in the higher eukaryotes that, once phosphorylated, promotes transcription of cAMP response element‐regulated genes. We have studied the mitochondrial import of CREB and its effect on the expression of mtDNA‐encoded proteins. [³⁵S]Methionine‐labelled CREB, synthesized in vitro in the Rabbit Reticulocyte Lysate system using a construct of the human cDNA, was imported into the matrix of isolated rat liver mitochondria by a membrane potential and TOM complex‐dependent process. The imported CREB caused cAMP‐dependent promotion of the synthesis of mitochondrially encoded subunits of oxidative phosphorylation enzyme complexes. Thus, CREB moves from the cytosol to mitochondria, in addition to the nucleus, and, when phosphorylated by cAMP‐dependent protein kinase, promotes the expression of mitochondrial genes.