Details

Autor(en) / Beteiligte

• del Arco, Araceli
• Contreras, Laura
• Pardo, Beatriz
• Satrustegui, Jorgina

Titel

Calcium regulation of mitochondrial carriers

Ist Teil von

• Biochimica et biophysica acta, 2016-10, Vol.1863 (10), p.2413-2421

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Mitochondrial function is regulated by calcium. In addition to the long known effects of matrix Ca2+, regulation of metabolite transport by extramitochondrial Ca2+ represents an alternative Ca2+-dependent mechanism to regulate mitochondrial function. The Ca2+ regulated mitochondrial transporters (CaMCs) are well suited for that role, as they contain long N-terminal extensions harboring EF-hand Ca2+ binding domains facing the intermembrane space. They fall in two groups, the aspartate/glutamate exchangers, AGCs, major components of the NADH malate aspartate shuttle (MAS) and urea cycle, and the ATP-Mg2+/Pi exchangers or short CaMCs (APCs or SCaMCs). The AGCs are activated by relatively low Ca2+ levels only slightly higher than resting Ca2+, whereas all SCaMCs studied so far require strong Ca2+ signals, above micromolar, for activation. In addition, AGCs are not strictly Ca2+ dependent, being active even in Ca2+-free conditions. Thus, AGCs are well suited to respond to small Ca2+ signals and that do not reach mitochondria. In contrast, ATP-Mg2+/Pi carriers are inactive in Ca2+ free conditions and activation requires Ca2+ signals that will also activate the calcium uniporter (MCU). By changing the net content of adenine nucleotides of the matrix upon activation, SCaMCs regulate the activity of the permeability transition pore, and the Ca2+ retention capacity of mitochondria (CRC), two functions synergizing with those of the MCU. The different Ca2+ activation properties of the two CaMCs are discussed in relation to their newly obtained structures. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. •Ca2+ regulated mitochondrial carriers (CaMCs) transduce Ca2+ signals to mitochondria.•CaMCs comprise aspartate/glutamate (AGCs) and ATP-Mg/Pi (SCaMCs, APCs) carriers.•AGCs are active at basal Ca2+, and require small Ca2+ signals for further activation.•These small Ca2+ signals do not need to reach the mitochondrial matrix.•SCaMCs are activated by large Ca2+ signals that also reach the matrix.