A biphasic increment of intracellular free Ca²⁺ levels is the primary signal of T lymphocyte activation after antigen recognition, as consequence of Ca²⁺ emptying of InsP₃-sensitive stores and the Ca²⁺ entry through a store-operated Ca²⁺ channel type known as CRAC (Ca²⁺-release activated Ca²⁺). As occurs with other Ca²⁺ channels, CRAC inactivates in a Ca²⁺-dependent manner so that any mechanism that regulates cytoplasmic Ca²⁺ concentration could also modulate CRAC channels activity. In this context, by serving as intracellular Ca²⁺ buffers, mitochondria have been proposed to control CRAC current (I_CRAC). However, mitochondria can also regulate I_CRAC by a distinct mechanism from direct buffering of Ca²⁺, such as the release of a soluble factor that we have identified as ATP. Using the whole cell configuration of patch-clamp technique, which permits the control of the intracellular environment, we have investigated the involvement of subplasmalemmal mitochondria in the regulation of Ca²⁺ microdomains and hence, I_CRAC characteristics. Our results indicate that energized mitochondria regulate slow Ca²⁺-dependent inactivation of I_CRAC by increasing subplasmalemmal Ca²⁺ buffering capacity mainly through a localized ATP production and support the idea of a functional relationship between CRAC channels and peripheral mitochondria. We also will discuss preliminary results about the role played by the composition of plasma membrane in the activity of CRAC channels and the role played by another elements to exert a local control in the activity of CRAC channels.