Prohibitins: A Critical Role in Mitochondrial Functions and Implication in Diseases

Abstract

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.

Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines

“…A recent study by our group established that the pan-PAD inhibitor Cl-amidine reduced deimination of the mitochondrial house-keeping protein prohibitin (PHB) and deimination of histone H3, as well as identifying a range of protein candidates that are deiminated in LN18 and LN229 cells under normal growth conditions [9]. This included prohibitin (PHB), a multifaceted protein with key roles in mitochondrial housekeeping and tumorigenesis [41][42][43][44]; Stromal interaction molecule 1 (STIM-1) which is a membrane ER-resident protein with important roles in calcium-homeostasis and cancer invasion [45][46][47]; and moesin, a critical factor for cell migration, filopodia formation [48] and associated with more aggressive forms of GBM [49,50]. The assessment of proteins involved in mitochondrial function, cancer progression and invasion is of considerable relevance both with respect to PAD-inhibitor mediated changes in total protein levels and with respect to their post-translational deimination, as this may affect protein structure, function and protein-protein interactions [1,40].…”

PBMC of Multiple Sclerosis Patients Show Deregulation of OPA1 Processing Associated with Increased ROS and PHB2 Protein Levels

“…Furthermore, OPA1 processing and stability is also controlled by PHB2 protein. In mitochondrial inner membrane, PHB2 protein forms with PHB1 a large membrane-bound complex [40,41]. This complex is required for OPA1 stability [42], indeed the deletion of PHB2 leads to the impaired cellular proliferation, aberrant mitochondrial cristae morphogenesis, and apoptosis [24,42], while an over-expression of PHB2 is reported to protect cells from apoptosis [43].…”

Identification of HeLa cell proteins that interact with Chlamydia�trachomatis glycogen synthase using yeast two‑hybrid assays

“…PHB2 can translocate from the mitochondria to the nucleus during capsaicin-induced apoptosis (28). PHB1 and 2 are conserved mitochondrial proteins with diverse functions, which include roles in cell proliferation and mitochondrial integrity (29). as obligate intracellular pathogens, chlamydia have been proposed to be anti-apoptotic to complete their development cycle (30).…”