Mitochondrial Ca2+ in B cell signaling and metabolism

钙（Ca2+）是一种多功能的第二信使，已知可以控制B细胞命运决定的各种细胞内信号通路。此外，Ca2+也是诱导凋亡的效应分子，并通过增强几种代谢酶的活性在细胞生物能量学中发挥作用。在静止的B细胞中，Ca2+被隔离在内质网（ER）中，并在B细胞受体刺激后迅速进入细胞质，激活Ca2+依赖的信号转导。内质网可以通过专门的接触位点与线粒体相互作用，并交换包括Ca2+在内的小分子。线粒体含有大量的Ca2+，但线粒体Ca2+在B细胞中的确切作用目前尚不清楚。在我们的初步结果中，我们发现内质网线粒体接触位点的形成和线粒体钙的摄取受细胞激活以及代谢和内质网应激的控制。反过来，我们发现线粒体Ca2+水平的变化会影响B细胞信号传导、线粒体活性、增殖和存活。我们现在的目标是识别在刺激和压力下协调er -线粒体相互作用和线粒体Ca2+稳态的信号分子。此外，我们试图剖析线粒体Ca2+依赖性调节B细胞功能的分子机制。鉴于Ca2+在B细胞中发挥的多种作用，更好地了解线粒体Ca2+调节提供了在未来确定治疗B细胞源性疾病的新靶点的可能性。

Calcium (Ca2+) is a versatile second messenger known to govern various intracellular signaling pathways central to B cell fate decisions. Additionally, Ca2+ is also an effector molecule in apoptosis induction and plays a role in cellular bioenergetics by enhancing the activity of several metabolic enzymes. In resting B cells, Ca2+ is sequestered in the endoplasmic reticulum (ER) and enters the cytosol quickly after B cell receptor stimulation to activate Ca2+ dependent signal transduction. The ER can interact with the mitochondria through dedicated contact sites and exchange small molecules including Ca2+. Mitochondria harbour significant amounts of Ca2+, yet the exact role of mitochondrial Ca2+ in B cells is currently poorly understood. In our preliminary results we have found that the formation of ER-mitochondria contact sites and mitochondrial calcium uptake are governed by cellular activation as well as metabolic and ER stress. In turn, we have found changes in mitochondrial Ca2+ levels to affect B cell signaling, mitochondrial activity, proliferation and survival. Our goal now is to identify signaling molecules orchestrating ER-mitochondria interactions and mitochondrial Ca2+ homeostasis in response to stimulation and stress. Moreover, we seek to dissect the molecular mechanisms of mitochondrial Ca2+ -dependent regulation of B cell function. Given the versatile role Ca2+ plays in B cells, a better understanding of mitochondrial Ca2+ regulation offers the possibility to identify new targets for treatment of B cell derived disorders in the future.