Mitochondrial dynamics and their impact on T cell function

作者：Quintana Ariel; Hoth Markus^*

来源：Cell Calcium, 2012, 52(1): 57-63.

DOI：10.1016/j.ceca.2012.02.005

• Mitochondria
• Calcium
• Transport
• Fusion
• Fission
• Tethering
• Endoplasmic reticulum
• CRAC
• ORAI
• PMCA
• Calcium microdomain
• T cells
• T lymphocytes
• Immune synapse

Energy supply is the most prominent function of mitochondria, but in addition, mitochondria are indispensable for a multitude of other important cellular functions including calcium (Ca2+) signaling and buffering, the supply of metabolites and the sequestration of apoptotic factors. The efficiency of those functions highly depends on the proper positioning of mitochondria within the cytosol. In lymphocytes, mitochondria preferentially localize into the vicinity (similar to 200 nm) of the immune synapse (IS). This localization is regulated by motor-based cytoskeleton-mediated transport, the fusion/fission dynamics of mitochondria, and probably also through tethering with the ER. IS formation also induces the accumulation of CRAC/ORAI1 Ca2+ channels, the CRAC/ORAI channel activator STIM1, K+ channels and plasma membrane Ca2+ ATPase (PMCA) within the IS. Such a large agglomeration of Ca2+ binding organelles and proteins highlights the IS as a critical cellular compartment for Ca2+ dependent lymphocyte activation. At the IS, Ca2+ microdomains generated beneath open CRAC/ORAI channels provide a rapid, robust and reliable mechanism for driving cellular responses in mast cells and T cells. Here, we discuss the relevance of motor-based mitochondrial transport, fusion, fission and tethering for mitochondrial localization in T cells and the importance of subplasmalemmal mitochondria to control local CRAC/ORAI1-dependent Ca2+ microdomains at the IS for efficient T lymphocyte activation.

• 出版日期2012-7