Mitochondrial Dysfunction
Mitochondria are central hubs of cellular metabolism, energy production, and redox balance. Beyond generating ATP, they play essential roles in lipid oxidation, calcium homeostasis, apoptosis regulation, and metabolic signaling. In the context of metabolic diseases such as obesity, type 2 diabetes, fatty liver disease, and chronic kidney disease, mitochondrial dysfunction contributes to impaired tissue function and disease progression.
Disruptions in mitochondrial oxidative phosphorylation, membrane potential, dynamics (fission/fusion), and biogenesis result in reduced energy efficiency, increased reactive oxygen species (ROS), and the activation of pro-inflammatory and pro-fibrotic signaling pathways.
Our lab is uncovering how the endocannabinoid system, and specifically the CB1R, modulates mitochondrial function in health and disease. Mounting evidence suggests that CB1R activation impairs mitochondrial respiration, alters mitochondrial morphology, and disrupts cellular energy homeostasis, while CB1R blockade reverses many of these deleterious effects.
We aim to define:
-
How CB1R influences mitochondrial dynamics, particularly the machinery regulating fission and fusion
-
The distinct roles of mitochondrial-localized CB1R vs. plasma membrane CB1R in shaping mitochondrial architecture and function
-
The contribution of CB1R to mitochondrial dysfunction in liver, kidney, adipose tissue, and its downstream metabolic consequences
In doing so, we seek to determine whether mitochondria-targeted CB1R modulation can serve as a novel therapeutic avenue to restore cellular and systemic energy balance.
Mitochondria as a Signaling Node for Inter-Organ Crosstalk
Beyond their cellular role, mitochondria participate in organ-to-organ communication via release of metabolites, ROS, and mitokines. Our work further explores how mitochondrial proteins such as adenine nucleotide translocator 2 (ANT2) regulate mitochondrial ATP/ADP exchange, whole-cell energy sensing, organelle stress responses, and crosstalk between kidney, liver, adipose tissue, and bone.
By studying how mitochondrial CB1R and ANT2 influence both intra- and inter-organ metabolic coordination, we aim to redefine mitochondria not just as powerhouses of the cell, but as central regulators of systemic metabolic health.
