Pathophysiological Significance of Calcium Signaling at Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs)

Efficient inter-organelle communication is critical for maintaining cellular physiology and driving cell functions. Endoplasmic reticulum (ER) is involved several such inter-organellar crosstalk with mitochondria, lysosomes, golgi complex, endosomes and peroxisomes. The functional tethering of ER and mitochondria at Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) provides a signaling hotspot for transfer of lipid and calcium (Ca²⁺) across these organelles. In last two decades, vital role for Ca²⁺ signaling at MAMs has been demonstrated in driving cell physiology. Recent studies have demonstrated that perturbations in Ca²⁺ signaling at MAMs lead to pathophysiological conditions such as cardiovascular diseases, metabolic disorders, cancers and neurodegenerative conditions. In this review, we discussed the key MAMs constituents that regulate Ca²⁺ signaling at these sites. Further, we retrospected the literature demonstrating role of Ca²⁺ dynamics at MAMs in human pathophysiology and highlighted major unanswered questions.

Laboratory of Calciomics and Systemic Pathophysiology, Regional Centre for Biotechnology (RCB), Faridabad, Delhi-NCR, India

For full article: https://www.sciencedirect.com/science/article/pii/S2468867320300973