Mitochondrial transporters as novel targets for intracellular calcium signaling.
Ca(2+) signaling in mitochondria is important to tune mitochondrial function to a variety of extracellular stimuli. The main mechanism is Ca(2+) entry in mitochondria via the Ca(2+) uniporter followed by Ca(2+) activation of three dehydrogenases in the mitochondrial matrix. This results in increases in mitochondrial NADH/NAD ratios and ATP levels and increased substrate uptake by mitochondria. We review evidence gathered more than 20 years ago and recent work indicating that substrate uptake, mitochondrial NADH/NAD ratios, and ATP levels may be also activated in response to cytosolic Ca(2+) signals via a mechanism that does not require the entry of Ca(2+) in mitochondria, a mechanism depending on the activity of Ca(2+)-dependent mitochondrial carriers (CaMC). CaMCs fall into two groups, the aspartate-glutamate carriers (AGC) and the ATP-Mg/P(i) carriers, also named SCaMC (for short CaMC). The two mammalian AGCs, aralar and citrin, are members of the malate-aspartate NADH shuttle, and citrin, the liver AGC, is also a member of the urea cycle. Both types of CaMCs are activated by Ca(2+) in the intermembrane space and function together with the Ca(2+) uniporter in decoding the Ca(2+) signal into a mitochondrial response.
Satrústegui
Jorgina
J
Departamento de Biología Molecular Centro de Biología Molecular "Severo Ochoa" UAM-CSIC, Facultad de Ciencias, Universidad Autónoma, Madrid, Spain. jsatrustegui@cbm.uam.es
Pardo
Beatriz
B
Del Arco
Araceli
A
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*
D033681:Mitochondrial Membrane Transport Proteins