Studying mitochondrial Ca(2+) uptake - a revisit.

Mitochondrial Ca(2+) sequestration is a well-known process that is involved in various physiological and pathological mechanisms. Using isolated suspended mitochondria one unique mitochondrial Ca(2+) uniporter was considered to account ubiquitously for the transfer of Ca(2+) into these organelles. However, by applying alternative techniques for measuring mitochondrial Ca(2+) uptake evidences for molecularly distinct mitochondrial Ca(2+) carriers accumulated recently.

Uncoupling protein 3 adjusts mitochondrial Ca(2+) uptake to high and low Ca(2+) signals.

Uncoupling proteins 2 and 3 (UCP2/3) are essential for mitochondrial Ca(2+) uptake but both proteins exhibit distinct activities in regard to the source and mode of Ca(2+) mobilization. In the present work, structural determinants of their contribution to mitochondrial Ca(2+) uptake were explored. Previous findings indicate the importance of the intermembrane loop 2 (IML2) for the contribution of UCP2/3.

The contribution of UCP2 and UCP3 to mitochondrial Ca(2+) uptake is differentially determined by the source of supplied Ca(2+).

The transmission of Ca(2+) signals to mitochondria is an important phenomenon in cell signaling. We have recently reported that the novel uncoupling proteins UCP2 and UCP3 (UCP2/3) are fundamental for mitochondrial Ca(2+) uniport (MCU). In the present study we investigate the contribution of UCP2/3 to mitochondrial accumulation of Ca(2+) either exclusively released from the ER or entering the cell via the store-operated Ca(2+) entry (SOCE) pathway.

Mitochondrial Ca2+, the secret behind the function of uncoupling proteins 2 and 3?

The underlying molecular action of the novel uncoupling proteins 2 and 3 (UCP2 and UCP3) is still under debate. The proteins have been implicated in many cell functions, including the regulation of insulin secretion and regulation of reactive oxygen species (ROS) generation. These effects have mainly been explained by suggesting that the proteins establish a proton leak through the inner mitochondrial membrane (IMM).

Uncoupling proteins 2 and 3 are fundamental for mitochondrial Ca2+ uniport.

Mitochondrial Ca(2+) uptake is crucial for the regulation of the rate of oxidative phosphorylation, the modulation of spatio-temporal cytosolic Ca(2+) signals and apoptosis. Although the phenomenon of mitochondrial Ca(2+) sequestration, its characteristics and physiological consequences have been convincingly reported, the actual protein(s) involved in this process are unknown. Here, we show that the uncoupling proteins 2 and 3 (UCP2 and UCP3) are essential for mitochondrial Ca(2+) uptake.

Import and fate of fluorescent analogs of oxidized phospholipids in vascular smooth muscle cells.

Lipid oxidation is now thought to be an initiating and sustaining event in atherogenesis. Oxidatively fragmented phospholipids, namely 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), present in minimally modified LDL and atherosclerotic lesions, have been reported to elicit a wide range of pathophysiological responses in the cells of the vascular wall. Nevertheless, the question of their potential sites of action and their primary molecular targets remains open.

The role of mitochondria for Ca2+ refilling of the endoplasmic reticulum.

Endoplasmic reticulum (ER) Ca2+ refilling is an active process to ensure an appropriate ER Ca2+ content under basal conditions and to maintain or restore ER Ca2+ concentration during/after cell stimulation. The mechanisms to achieve successful ER Ca2+ refilling are multiple and built on a concerted action of processes that provide a suitable reservoir for Ca2+ sequestration into the ER. Despite mitochondria having been found to play an essential role in the maintenance of capacitative Ca2+ entry by buffering subplasmalemmal Ca2+, their contribution to ER Ca2+ refilling was not subjected to detailed analysis so far.