Mitochondrial calcium homeostasis as a key regulator of the calcium dependent immune response

• Applicant: Dr. Ariel Quintana-González
• Subject Area: Immunology
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 136006733

Calcium (Ca2+) is a ubiquitous intracellular signal responsible for controlling numerous cellular processes. Its enormous versatility is achieved through the interaction with other signaling pathways. In addition to their well-known functions in cellular energy transduction, mitochondria can rapidly take up and slowly release large amounts of Ca2+, enabling them not only to protect cells against cytosolic Ca2+ overload under pathophysiological conditions but also to shape and prolong physiological Ca2+ signals. Sustained Ca2+ influx through plasma membrane Ca2+ released-activated Ca2+ (CRAC) channels is crucial for the activation of immune cells and the subsequent immune response. Therefore, it is not surprising that perturbations in the function and/or activation of CRAC channels have the potential for immune pathological outcomes. Recently, mitochondrial Ca2+ uptake has been reported to be essential for sustaining the activity of CRAC channels by preventing local Ca2+ accumulation near sites that govern channel inactivation. However, despite the importance of mitochondrial Ca2+ homeostasis for cell function, the molecular identity of mitochondrial Ca2+ uptake is still completely unknown. Thus, my project focuses on finding, identifying and characterizing the mitochondrial Ca2+ homeostasis regulators by using the novel and powerful genome-wide RNA interfering screen methodology. The identification of these molecules will provide new insights that help to understand better the crucial role of mitochondria in the complex molecular mechanism of cellular Ca2+ homeostasis.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Dr. Anjana Rao