[Frontiers in Bioscience S5, 198-205, January 1, 2013]

Cytosolic (pro)renin and the matter of intracellular renin actions

Jorg Peters1

1Institute of Physiology, University of Greifswald, Greifswalder Str. 11C, D-17495 Karlsburg, Germany


1. Abstract
2. Introduction
3. Previously unrecognized renin transcripts encode a cytosolic renin isoform
4. Differential regulation and tissue-specific expression of renin transcripts
5. Functions of cytosolic (pro)renin
6. Mechanism of action of intracellular renin
6.1. ANG II and its effects in cytosol, mitochondria and nuclei
6.1.1. Cytosolic, intra-mitochondrial or nuclear angiotensin generation: supporting data
6.1.2. Cytosolic, intra-mitochondrial or nuclear angiotensin generation: open questions
6.2. ANG II-independent effects of renin in cytosol, mitochondria and nuclei
7. Conclusions
8. Acknowledgement
9. References


Renin is known as a secretory glycoprotein produced, stored and released by the kidney. Renin cleaves angiotensin (ANG) I from angiotensinogen, which is further cleaved to ANG II by ANG-converting enzyme. ANG II acts via specific receptors located at the cell membrane. Recently renin transcripts have been discovered which encode a cytosolic protein that cannot be secreted. These transcripts are derived from the same renin gene but probably use another promoter located within intron A. Whereas the kidney exclusively expresses the transcript encoding secretory renin, other tissues additionally or exclusively express transcripts encoding cytosolic renin. The cytosolic renin protein exerts functions different and even opposite to those of secretory renin. Whereas secretory renin increases necrotic death rates of cardiac cells, the cytosolic renin isoform even protects cells from necrotic death. This review describes the properties of cytosolic renin and its cellular functions and discusses possible mechanisms of actions particularly in the light of the discovery of direct nuclear and mitochondrial effects of ANG' s.