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Cannabinoid-1 receptor regulates mitochondrial dynamics and function in renal proximal tubular cells.
- Source :
-
Diabetes, obesity & metabolism [Diabetes Obes Metab] 2019 Jan; Vol. 21 (1), pp. 146-159. Date of Electronic Publication: 2018 Sep 10. - Publication Year :
- 2019
-
Abstract
- Aims: To evaluate the specific role of the endocannabinoid/cannabinoid type-1 (CB <subscript>1</subscript> R) system in modulating mitochondrial dynamics in the metabolically active renal proximal tubular cells (RPTCs).<br />Materials and Methods: We utilized mitochondrially-targeted GFP in live cells (wild-type and null for the CB <subscript>1</subscript> R) and electron microscopy in kidney sections of RPTC-CB <subscript>1</subscript> R <superscript>-/-</superscript> mice and their littermate controls. In both in vitro and in vivo conditions, we assessed the ability of CB <subscript>1</subscript> R agonism or fatty acid flux to modulate mitochondrial architecture and function.<br />Results: Direct stimulation of CB <subscript>1</subscript> 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. CB <subscript>1</subscript> 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 CB <subscript>1</subscript> R-dependent mitochondrial fission, lipotoxicity and cellular dysfunction.<br />Conclusions: CB <subscript>1</subscript> R plays a key role in inducing mitochondrial fragmentation in RPTCs, leading to a decline in the organelle's function and contributing to the renal tubular injury associated with lipotoxicity and other metabolic diseases.<br /> (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
Details
- Language :
- English
- ISSN :
- 1463-1326
- Volume :
- 21
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Diabetes, obesity & metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 30091204
- Full Text :
- https://doi.org/10.1111/dom.13497