PHB blocks endoplasmic reticulum stress and apoptosis induced by MPTP/MPP+ in PD models

The Mitochondrial PHB Complex Determines Lipid Composition and Interacts With the Endoplasmic Reticulum to Regulate Ageing

“…However, although PHB-depletion did not further induce the UPR ER in the presence of tunicamycin, an ER stressor, in its absence phb-2(RNAi) induced the UPR ER ( Bennett et al, 2014 ). Moreover, PHB overexpression has been recently shown to block ER stress in a mice model of Parkinson’s disease ( Wang et al, 2021 ). Importantly, PHB genetically interacts with genes involved in mitochondria-ER contact sites ( Kornmann et al, 2009 ), which are important for transferring PLs ( Senft and Ronai, 2015 ; Phillips and Voeltz, 2016 ).…”

The function of prohibitins in mitochondria and the clinical potentials

“…The authors also studied the content of ATP synthase in each tissue and found that the correlation between PHBs level and PHBs content is not single, which suggests different signal regulation of inhibition and ATP synthase is prohibited, but the reason for the normal levels of ATP synthase in the frontal cortex of pDLB is unclear. Over-expression of PHBs in the striatum blocked mitochondrial depolarization and motor dysfunction in PD mice, demonstrating that PHBs can affect neuroprotection and that increased PHBs levels protect dopaminergic neurons against mitochondrial ROS and cytotoxicity [58].…”

“…After the C-terminus of PHBs is knocked out, HCV are not able to infect hepatocytes. PHB1 is also involved in the entry of DENV-2 and chikungunya virus (CHIKV) [20], in which the complex of PHB1 and PHB2 is identified as the receptor of dengue virus into SH-SY5Y and Intestinal mucosal epithelial cells The receptor of some viruses [15][16][17][18] Hepatocytes Mediate the virus to enter [19] Renal cells Induce hydrolytic inactivation of OPA1 protein; decrease mitochondrial dynamics [45] Preadipocytes Mitochondrial dysfunction and down-regulation of adipogenesis [48,49] Heart cells Induce cardiac fatty acid metabolism disorders [50] Virus EV-A71 Reduce virus replication and the incidence of critical illness [86] COVID-19 Mediate the host immune evasion response [87] New coronary pneumonia Grant the ability of host immune evasion and virus replication [88] Diseases AD Regulate the mitochondrial oxidative stress response, reduce cognitive deficits [31] Protect dopaminergic neurons against mitochondrial ROS and cytotoxicity [58] HCV PHB-CRAF interaction [19] Triple-negative breast cancer Dissociate from DRP1; disrupt the mitochondrial membrane potential and triggering the apoptotic cascade [42] Gynecologic cancer Prevent cisplatin-induced mitochondrial division and Oma1-mediated cleavage as well as changes in OPA1 processing [46] Nasopharyngeal carcinoma Counteract TRIM21-mediated ubiquitination to inhibit the NF-κB activity [71] Hepatocellular carcinoma Down-regulate the regulatory proteins in the G0/G1 phase [72] Gastric cancer MAPK signaling pathway decreases the ubiquitination level of PHB1 [73,74] Colorectal carcinoma cells Inhibit Wnt/beta-catenin signaling [78] CHME-3 cells, and binds to the HIV-1 glycoprotein and envelope protein of leukoplakia syndrome virus [19].…”

Prohibitins in neurodegeneration and mitochondrial homeostasis

“…This suggest that PHB upregulation could be used as a protective mechanism against toxic insult, just as observed in neurons of PD-induced models (Park et al, 2010;Dutta et al, 2018). In dopaminergic SH-SY5Y cells treated with MPP + , overexpression of PHB restores mitochondrial membrane potential (≈2-fold increase as compared to control treated samples), decreases ROS (≈2-fold decrease) and reduces cytochrome c release (≈−0.8-fold decrease) (Dutta et al, 2018;Wang et al, 2021b), while knockdown of PHB increases the toxic effect (≈1.6-fold) of 6-OH as measured by cell viability (Park et al, 2010). Rotenone, another neurotoxin involved in mitochondrial complex I disruption, have been also associated with a protective role of PHB in PC12 cell cultures and rat primary neurons.…”