Canna~Fangled Abstracts

Cannabinoid-1 Receptor Regulates Mitochondrial Dynamics and Function in Renal Proximal Tubular Cells.

By August 9, 2018No Comments
2018 Aug 9. doi: 10.1111/dom.13497.
[Epub ahead of print]

Abstract

AIMS:

To evaluate the specific role of the endocannabinoid/CB1 R system in modulating mitochondrial dynamics in the metabolically active renal proximal tubular cells (RPTCs).

MATERIALS AND METHODS:

We utilized mitochondrialy-targeted GFP in live cells (wild-type and null for the CB1 R), and electron microscopy in kidney sections of RPTC-CB1 R-/- mice and their littermate controls. In both in vitro and in vivo conditions, we assessed the ability of CB1 R agonism or fatty acid flux to modulate mitochondrial architecture and function.

RESULTS:

Direct stimulation of CB1 R resulted in mitochondrial fragmentation in RPTCs. This process was mediated, at least in part, by modulating the phosphorylation levels of the canonical fission protein dynamin-related protein 1 on both S637 and S616 residues. CB1 R-induced mitochondrial fission was associated with mitochondrial dysfunction, as documented by reduced oxygen consumption and ATP production, increased reactive oxygen species and cellular lactate levels, as well as a decline in mitochondrial biogenesis. Likewise, we documented that exposure of RPTCs to a fatty acid flux induced CB1 R-depended mitochondrial fission, lipotoxicity, and cellular dysfunction.

CONCLUSIONS:

CB1 R plays a key role in inducing mitochondrial fragmentation in RPTCs, leading to a decline in organelle’s function, and contributing to renal tubular injury associated with lipotoxicity and other metabolic diseases. This article is protected by copyright. All rights reserved.