It has been known for a long time that isolated mitochondria are able to accumulate large amounts of calcium ions. Before the discovery that endoplasmic reticulum (ER) was the main Ca2+-storing cellular organelle, mitochondria were thought to play a major role in cytoplasmic Ca2+ homeostasis (Carafoli, 2002). After IP3 was discovered and it was shown that IP3 receptors were localized in ER membrane and that Ca2+-binding proteins such as calsequestrin could store large amounts of Ca2+ in the ER, the role of mitochondria in the regulation of cytoplasmic Ca2+ was questioned. However, in recent years, mostly due to the development of new methods, there has been increasing evidence that mitochondria could be an important cytoplasmic Ca2+ sink, especially under conditions of a high cellular Ca2+ load. Experimental Physiology (2003) 88.1, 91-97.