TRPV4 acts as a mitochondrial Ca2+-importer and regulates mitochondrial temperature and metabolism.

TRPV4 is associated with the development of neuropathic pain, sensory defects, muscular dystrophies, neurodegenerative disorders, Charcot Marie Tooth and skeletal dysplasia. In all these cases, mitochondrial abnormalities are prominent. Here, we demonstrate that TRPV4, localizes to a subpopulation of mitochondria in various cell lines. Improper expression and/or function of TRPV4 induces several mitochondrial abnormalities. TRPV4 is also involved in the regulation of mitochondrial numbers, Ca2+-levels and mitochondrial temperature. Accordingly, several naturally occurring TRPV4 mutations affect mitochondrial morphology and distribution. These findings may help in understanding the significance of mitochondria in TRPV4-mediated channelopathies possibly classifying them as mitochondrial diseases.