The role of prohibitin in cell signaling

Prohibitin-1 (PHB, also known as PHB1), a member of the Band-7 family of proteins, is highly conserved evolutionarily, widely expressed, and present in different cellular compartments. Genetic studies with different organism models have provided strong evidence for an important biological role of PHB in mitochondrial function, cell proliferation, and development. Recent discoveries regarding the involvement of PHB in phophatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) and transforming growth factor-beta (TGF-beta)/signal transducers and activators of transcription signaling pathways, and earlier reports on the interaction of PHB with Raf and its critical role in Ras/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling opened up the possibility that PHB has functions outside of the mitochondria (extramitochondrial) and may be a multifunctional protein. The PI3K/Akt and Ras/MAPK/ERK signaling cascades are versatile signaling processes that diverge from the same receptor tyrosine kinase root, and are involved in cell metabolism, proliferation, and development. Here, we review the emerging role of PHB and its post-translational modifications in signal transduction pathways, especially in PI3K/Akt and Ras/MAPK/ERK signaling. A recent discovery of opposing effects of PHB on longevity under different metabolic states and its potential connection with insulin/insulin-like growth factor-I signaling is also discussed.