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Amyloid precursor protein intracellular domain modulates cellular calcium homeostasis and ATP content
Author(s) -
Hamid Runa,
Kilger Ellen,
Willem Michael,
Vassallo Neville,
Kostka Markus,
Bornhövd Carsten,
Reichert Andreas S.,
Kretzschmar Hans A.,
Haass Christian,
Herms Jochen
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04627.x
Subject(s) - endoplasmic reticulum , mitochondrion , microbiology and biotechnology , homeostasis , bioenergetics , cytosol , intracellular , calcium signaling , chemistry , oxidative phosphorylation , amyloid precursor protein , calcium , biology , biochemistry , medicine , enzyme , disease , organic chemistry , alzheimer's disease
Consecutive cleavages of amyloid precursor protein (APP) generate APP intracellular domain (AICD). Its cellular function is still unclear. In this study, we investigated the functional role of AICD in cellular Ca 2+ homeostasis. We could confirm previous observations that endoplasmic reticulum Ca 2+ stores contain less calcium in cells with reduced APP γ‐secretase cleavage products, increased AICD degradation, reduced AICD expression or in cells lacking APP. In addition, we observed an enhanced resting cytosolic calcium concentration under conditions where AICD is decreased or missing. In view of the reciprocal effects of Ca 2+ on mitochondria and of mitochondria on Ca 2+ homeostasis, we analysed further the cellular ATP content and the mitochondrial membrane potential. We observed a reduced ATP content and a mitochondrial hyperpolarisation in cells with reduced amounts of AICD. Blockade of mitochondrial oxidative phosphorylation chain in control cells lead to similar alterations as in cells lacking AICD. On the other hand, substrates of Complex II rescued the alteration in Ca 2+ homeostasis in cells lacking AICD. Based on these observations, our findings indicate that alterations observed in endoplasmic reticulum Ca 2+ storage in cells with reduced amounts of AICD are reciprocally linked to mitochondrial bioenergetic function.