Mitochondria and Calcium Regulation as Basis of Neurodegeneration Associated With Aging

Frontiers in Neuroscience

Mario Sanhueza²  César Cárdenas⁴  Marioly Müller⁵  Ulises Ahumada-Castro⁶  Felipe A. Court⁷  Christian Gonzalez-Billault⁷ 

[1] Anatomy and Developmental Biology Program, Institute of Biomedical Sciences, University of Chile, Santiago, Chile;Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile;Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile;Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, United States;Department of Medical Technology, Faculty of Medicine, Universidad de Chile, Santiago, Chile;Geroscience Center for Brain Health and Metabolism, Santiago, Chile;The Buck Institute for Research on Aging, Novato, CA, United States;

关键词: mitochondria;    MAMS;    calcium;    neurodegeneration;    ROS;    MPTP;   

DOI  :  10.3389/fnins.2018.00470

来源: DOAJ

【 摘 要 】

Age is the main risk factor for the onset of neurodegenerative diseases. A decline of mitochondrial function has been observed in several age-dependent neurodegenerative diseases and may be a major contributing factor in their progression. Recent findings have shown that mitochondrial fitness is tightly regulated by Ca2+ signals, which are altered long before the onset of measurable histopathology hallmarks or cognitive deficits in several neurodegenerative diseases including Alzheimer’s disease (AD), the most frequent cause of dementia. The transfer of Ca2+ from the endoplasmic reticulum (ER) to the mitochondria, facilitated by the presence of mitochondria-associated membranes (MAMs), is essential for several physiological mitochondrial functions such as respiration. Ca2+ transfer to mitochondria must be finely regulated because excess Ca2+ will disturb oxidative phosphorylation (OXPHOS), thereby increasing the generation of reactive oxygen species (ROS) that leads to cellular damage observed in both aging and neurodegenerative diseases. In addition, excess Ca2+ and ROS trigger the opening of the mitochondrial transition pore mPTP, leading to loss of mitochondrial function and cell death. mPTP opening probably increases with age and its activity has been associated with several neurodegenerative diseases. As Ca2+ seems to be the initiator of the mitochondrial failure that contributes to the synaptic deficit observed during aging and neurodegeneration, in this review, we aim to look at current evidence for mitochondrial dysfunction caused by Ca2+ miscommunication in neuronal models of neurodegenerative disorders related to aging, with special emphasis on AD.

【 授权许可】

Unknown