2015/07/01

Prohibitins (PHBs) comprise an evolutionary conserved and ubiquitously expressed family of proteins with a variety of suggested activities in different cellular compartments

Prohibitins (PHBs) comprise an evolutionary conserved and ubiquitously expressed family of proteins with a variety of suggested activities in different cellular compartments. Given the implication of PHB1 in many vital functions, we generated a liver-specific Phb1 knockout (Phb1 KO) mice, which developed liver fibrosis spontaneously. In humans, reduced levels of PHB1 have been observed in obese people at risk of developing non-alcoholic steatohepatitis. The laboratory of Maria Luz Martinez Chantar in the Metabolomics Unit at CIC bioGUNE has described that PHB1 expression is markedly reduced in common human cholestatic liver diseases and provide the molecular basis underlying the PHB1's protective role in the liver. Importantly, we have data identified PHB1 as a critical modulator in cholestatic liver injury regulating HDAC4 activity and specific epigenetic marks. These results also confirm that HDAC4 activity is central during hepatic damage caused by PHB1 deficiency. This mechanism might be particularly important for the identification of novel therapeutic targets, including HDAC4, to treat liver injury and chronic cholestatic diseases.

This study was recently published in Hepatology.
Hepatology. 2015 Jun 25. doi: 10.1002/hep.27959.
http://www.ncbi.nlm.nih.gov/pubmed/26109312