Prohibitin 2-mediated mitophagy attenuates renal tubular epithelial cells injury by regulating mitochondrial dysfunction and NLRP3 inflammasome activation.

Abstract	Accumulating evidence demonstrates that mitochondrial dysfunction and inflammasome activation play a critical role in the pathogenesis of renal tubular injury through the production of reactive oxygen species and cytokines. Prohibitin 2 (PHB2) is a newly identified intracellular receptor of mitophagy (a type of autophagy) that mediates selective removal of damaged mitochondria, and it could possibly play a renoprotective role in kidney disease. In this study, we confirmed that autophagy is activated in tubular epithelial cells treated with angiotensin II and that inhibition of autophagy results in tubular cell injury. Strikingly, PHB2 knockdown reduced the level of mitophagy and augmented cell death, while overexpression of PHB2 provided protection against pyrin domain-containing protein 3 (NLRP3)-induced inflammatory pathways through amelioration of mitochondrial dysfunction. Our research is the first to experimentally demonstrate the role of PHB2 in renal proximal tubular cells and thereby to provide a better understanding of how autophagy modulates inflammation in renal tubules. These data highlight PHB2 as a therapeutic target in the future treatment of CKD.
Authors	Yao Xu, Jingjing Wang, Wangjie Xu, Feng Ding, Wei Ding
Journal	American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 316 Issue 2 Pg. F396-F407 (02 01 2019) ISSN: 1522-1466 [Electronic] United States
PMID	30539655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Inflammasomes NLR Family, Pyrin Domain-Containing 3 Protein NLRP3 protein, human PHB2 protein, human Prohibitins Repressor Proteins Angiotensin II
Topics	Angiotensin II (toxicity) Apoptosis (drug effects) Cell Line Epithelial Cells (drug effects, metabolism, pathology) Humans Inflammasomes (drug effects, metabolism) Kidney Tubules, Proximal (drug effects, metabolism, pathology) Mitochondria (drug effects, metabolism, pathology) Mitophagy (drug effects) NLR Family, Pyrin Domain-Containing 3 Protein (metabolism) Prohibitins Repressor Proteins (genetics, metabolism) Signal Transduction

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!