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TRPV4 regulates mitochondrial Ca-status and physiology in primary murine T cells based on their immunological state. | LitMetric

TRPV4 regulates mitochondrial Ca-status and physiology in primary murine T cells based on their immunological state.

Life Sci

National 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. Electronic address:

Published: April 2023

AI Article Synopsis

Article Abstract

T cell activation process is critically affected by temperature and intracellular Ca-signalling. Yet, the nature and the key molecules involved in such complex Ca-signalling is poorly understood. It is mostly assumed that ion channels present in the plasma membrane primarily regulate the cytosolic Ca-levels exclusively. TRPV4 is a non-selective Ca channel which can be activated at physiological temperature. TRPV4 is involved in several physiological, pathophysiological process as well as different forms of pain. Here we demonstrate that TRPV4 is endogenously expressed in T cell and is present in the mitochondria of T cells. TRPV4 activation increases mitochondrial Ca-levels, and alters mitochondrial temperature as well as specific metabolisms. The TRPV4-dependent increment in the mitochondrial Ca is context-dependent and not just passively due to the increment in the cytosolic Ca. Our work also indicates that mitochondrial Ca-level correlates positively with a series of essential factors, such as mitochondrial membrane potential, mitochondrial ATP production and negatively correlates with certain factors such as mitochondrial temperature. We propose that TRPV4-mediated mitochondrial Ca-signalling and other metabolisms has implications in the immune activation process including immune synapse formation. Our data also endorse the re-evaluation of Ca-signalling in T cell, especially in the light of mitochondrial Ca-buffering and in higher body temperature, such as in case of fever. Presence of TRPV4 in the mitochondria of T cell is relevant for proper and optimum immune response and may provide evolutionary adaptive benefit. These findings may also have broad implications in different pathophysiological process, neuro-immune cross-talks, and channelopathies involving TRPV4.

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Source
http://dx.doi.org/10.1016/j.lfs.2023.121493DOI Listing

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