Calcium and endoplasmic reticulum-mitochondria tethering in neurodegeneration.

Tito Calì, Denis Ottolini, Marisa Brini

Department of Comparative Biomedicine and Food Science, University of Padova, Padova, Italy. tito.cali@unipd.it

DNA and cell biology 2013 Apr

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Mitochondria are key players of many physiological processes and deregulation of mitochondrial and/or mitochondria-related activity is unequivocally associated to numerous ageing-linked neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). Recently, the endoplasmic reticulum (ER) stress condition is emerging as a common feature relevant to the pathogenesis of this type of diseases. Mitochondria and ER are two compartments physically and functionally tightly interconnected and recent evidence revealed that the impairment in their communication might represent a common hit in different neurodegenerative diseases. ER-mitochondria contact sites are crucial for Ca(2+) signaling since, upon the opening of ER Ca(2+) release channels, microdomains of high [Ca(2+)] are generated in their proximity and Ca(2+) can be taken up by the low-affinity mitochondrial uniporter. This transfer is essential in stimulated as well as in resting conditions to sustain cell metabolism and bioenergetics. Alterations in the ER-mitochondria juxtaposition are critical not only because they determine mitochondrial dysfunctions, but also because they compromise lipid metabolism, protein synthesis, and folding, thus demonstrating that the interaction between the two compartments is bi-functional. However, the functional consequences of these alterations on Ca(2+) signaling and the possible involvement in the development of neurodegenerative conditions are currently largely unexplored. Here we will survey the recent literature in the field and discuss recent insights focusing on some cellular models expressing mutant proteins involved in the pathogenesis of familial forms of PD, AD, and ALS.

Citation

Tito Calì, Denis Ottolini, Marisa Brini. Calcium and endoplasmic reticulum-mitochondria tethering in neurodegeneration. DNA and cell biology. 2013 Apr;32(4):140-6