Cannabinoid-1 receptor regulates mitochondrial dynamics and function in renal proximal tubular cells

Diabetes Obes Metab. 2019 Jan;21(1):146-159. doi: 10.1111/dom.13497. Epub 2018 Sep 10.


Aims: To evaluate the specific role of the endocannabinoid/cannabinoid type-1 (CB1 R) system in modulating mitochondrial dynamics in the metabolically active renal proximal tubular cells (RPTCs).

Materials and methods: We utilized mitochondrially-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-dependent mitochondrial fission, lipotoxicity and cellular dysfunction.

Conclusions: CB1 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.

Keywords: cannabinoids; cellular research; experimental pharmacology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Kidney Tubules, Proximal* / chemistry
  • Kidney Tubules, Proximal* / cytology
  • Kidney Tubules, Proximal* / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Mitochondria / metabolism*
  • Receptor, Cannabinoid, CB1 / metabolism*


  • CNR1 protein, mouse
  • Receptor, Cannabinoid, CB1