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MITOCHONDRIAL PHYSIOLOGYCalcium homeostasis and oxidative stress Due to their large negative membrane potential, mitochondria can accumulate significant amounts of Ca2+ provided that the ambient Ca2+ concentration is sufficiently high. The latter is achieved by close juxtaposition of these organelles against the endoplasmic reticulum (ER), which forms the major source of Ca2+ ions during cellular stimulation. The increase in mitochondrial Ca2+ concentration causes a boost in mitochondrial ATP production, thus allowing the rapid balancing of local energy demand.
Using a combination of luminometry (cell groups) and digital imaging microscopy (single cells), we have found that Ca2+-stimulated mitochondrial ATP production is decreased in skin fibroblasts of patients with inherited complex I deficiency and that this decrease is mainly due to a pathological reduction in ER Ca2+ content. Thus far, we have shown that drugs that normalize the agonist-induced increase in mitochondrial Ca2+ concentration also normalize the agonist-induced increase in mitochondrial ATP production.
Members
John Esseling, PhD Peggy Roestenberg, PhD
Federica Valsecchi, Msc.
Ganesh Manjeri, Msc.
Sjenet van Emst-De Vies, ing.
Herman Swarts, ing.
MITOCHONDRIAL PHYSIOLOGY | ||
