Related Experiment Video
Updated: Aug 24, 2025
Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4
Published on: December 31, 2013
TRPV4 interacts with MFN2 and facilitates endoplasmic reticulum-mitochondrial contact points for Ca2+-buffering
Tusar Kanta Acharya1, Ashutosh Kumar1, Shamit Kumar1
1National Institute of Science Education and Research Bhubaneswar, School of Biological Sciences, P.O. Jatni, Khurda 752050, Odisha, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094, India.
Aim:
Mitochondrial fission-fusion events, distribution, and Ca2+-buffering abilities are relevant for several diseases, yet are poorly understood events. TRPV4 channels are a group of thermosensitive ion channel which regulate cellular and mitochondrial Ca2+-level. The underlying mechanisms of the change in mitochondrial dynamics upon modulation of TRPV4 channel are ill explored.
Main Methods:
We have used TRPV4 expressing stable cell line CHO-K1-V4 and compared with CHO-K1-Mock as a control cell. We have also used mouse bone marrow derived mesenchymal stem cells and purified mitochondria from mouse brain for the interaction study.
Key Findings:
Now we demonstrate that expression and/or pharmacological modulation of TRPV4 regulates mitochondrial morphologies and Ca2+-level. TRPV4 interacts with MFN1/MFN2, the mitochondrial regulatory factors. TRPV4 regulates ER-mito contact points. We used different cellular conditions where cytosolic or ER Ca2+-levels were pharmacologically altered. Analysis of ∼55,000 mitochondrial particles, ∼125,000 ER-mito contact points from ∼900 cells in 10 different cellular conditions suggest that ER-mito contact points are inversely regulated with mitochondrial Ca2+-levels where TRPV4 always elevates mitochondrial Ca2+-levels. These findings link TRPV4 with MFN2-mediated diseases and suggest that different TRPV4-induced channelopathies are likely due to mitochondrial abnormalities.
Insights
Transient Receptor Potential Vanilloid 4 (TRPV4) channels regulate mitochondrial calcium levels and dynamics. This study shows TRPV4 interacts with mitochondrial factors, influencing cell health and potentially causing channelopathies.
Area of Science:
- Mitochondrial biology
- Ion channel function
- Cellular physiology
Background:
- Mitochondrial dynamics and calcium (Ca2+) buffering are crucial in disease but poorly understood.
- Transient Receptor Potential Vanilloid 4 (TRPV4) channels influence cellular and mitochondrial Ca2+ levels.
- Mechanisms linking TRPV4 modulation to mitochondrial dynamics require further exploration.
Purpose of the Study:
- To investigate how TRPV4 channel activity affects mitochondrial morphology and Ca2+ handling.
- To explore the interaction between TRPV4 and mitochondrial regulatory proteins.
- To understand the role of TRPV4 in regulating endoplasmic reticulum (ER)-mitochondria contact points.
Main Methods:
- Utilized TRPV4-expressing (CHO-K1-V4) and control (CHO-K1-Mock) cell lines.
- Employed mouse bone marrow-derived mesenchymal stem cells and purified mouse brain mitochondria.
- Analyzed mitochondrial morphology, Ca2+ levels, and ER-mitochondria contacts across various cellular Ca2+ conditions.
Main Results:
- TRPV4 expression and modulation significantly alter mitochondrial morphology and Ca2+ levels.
- TRPV4 directly interacts with mitochondrial fission/fusion factors MFN1 and MFN2.
- TRPV4 regulates ER-mitochondria contact points, inversely correlating with mitochondrial Ca2+ levels.
- TRPV4 consistently increases mitochondrial Ca2+ levels.
Conclusions:
- TRPV4 plays a key role in regulating mitochondrial dynamics and Ca2+ homeostasis.
- Findings link TRPV4 to MFN2-mediated diseases.
- Mitochondrial abnormalities may underlie various TRPV4-induced channelopathies.
More Related Videos
08:27Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays
Published on: October 20, 2023
13:40Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
Published on: July 7, 2011
Related Concept Videos
01:37Energy to Drive Translocation
Generally, polypeptides are unfolded by two distinct...
01:19Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
01:45Vesicular Tubular Clusters
With the help of motor proteins such...
01:16Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:28Protein Translocation Machinery on the ER Membrane
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
01:29Insertion of Multi-pass Transmembrane Proteins in the RER
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...