Prohibitin 2: At a communications crossroads

Abstract

Prohibitins (PHBs) are a highly conserved class of proteins first discovered as inhibitors of cellular proliferation. Since then PHBs have been found to have a significant role in transcription, nuclear signaling, mitochondrial structural integrity, cell division, and cellular membrane metabolism, placing these proteins among the key regulators of pathologies such as cancer, neuromuscular degeneration, and other metabolic diseases. The human genome encodes two PHB proteins, prohibitin 1 (PHB1) and prohibitin 2 (PHB2), which function not only as a heterodimeric complex, but also independently. While many previous reviews have focused on the better characterized prohibitin, PHB1, this review focuses on PHB2 and new data concerning its cellular functions both in complex with PHB1 and independent of PHB1. V C 2015 IUBMB Life, 67(4): [239][240][241][242][243][244][245][246][247][248][249][250][251][252][253][254] 2015

How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways

“…At first sight this appears unexpected as Prohibitin 2 is located in the MIM as a part of the ring-shaped, heterodimeric Prohibitin 1/2 mega-complex which has important roles in mitochondrial biogenesis including degradation of mitochondrial membrane proteins, controlling mitochondrial protein folding, and cristae morphogenesis (reviewed in ArtalSanz and Tavernarakis, 2009;Bavelloni et al, 2015). Prohibitin 2 was shown to bind LC3-II, but not GABARAP with its LIR motif in a Pink1/Parkin-dependent manner and knockdown of the protein inhibited mitochondrial degradation (Wei et al, 2017).…”

PACT/PRKRA and p53 regulate transcriptional activity of DMRT1

“…Rather, the result suggested that each protein might be indirectly associated with DMRT1 through other DMRT1-binding proteins. PHB2 is an intercellular communicator between nucleus and mitochondria, and suppresses transcription of target genes in nuclei (Bavelloni et al, 2015). In contrast, the transcription factor YB-1 is involved in transcriptional regulation by interacting with other transcription factors, including p53 (Okamoto et al, 2000).…”

Targeted OMA1 therapies for cancer

“…Most observations, however, are in agreement with a model in which mitochondrial prohibitins exert an OMA1‐inhibitory function that protects cells from apoptosis and cell death. The intracellular distribution of the prohibitins is controlled by posttranslational modifications as well as protein–protein interactions between PHB, PHB2 and other proteins, including p53 …”

“…The intracellular distribution of the prohibitins is controlled by posttranslational modifications as well as protein-protein interactions between PHB, PHB2 and other proteins, including p53. 202,204,235 Tumor protein p53 p53 can promote cytochrome c release through OMA1dependent OPA1 cleavage. 169 p53 is a transcription factor with the capacity to suppress tumor growth.…”