Therapeutic Strategies Targeting Mitochondrial Calcium Signaling: A New Hope for Neurological Diseases?
Por:
Rodríguez LR, Lapeña-Luzón T, Benetó N, Beltran-Beltran V, Pallardó FV, Gonzalez-Cabo P and Navarro JA
Publicada:
15 ene 2022
Resumen:
Calcium (Ca 2+ ) is a versatile secondary messenger involved in the regulation of a plethora of different signaling pathways for cell maintenance. Specifically, intracellular Ca 2+ homeostasis is mainly regulated by the endoplasmic reticulum and the mitochondria, whose Ca 2+ exchange is mediated by appositions, termed endoplasmic reticulum-mitochondria-associated membranes (MAMs), formed by proteins resident in both compartments. These tethers are essential to manage the mitochondrial Ca 2+ influx that regulates the mitochondrial function of bioenergetics, mitochondrial dynamics, cell death, and oxidative stress. However, alterations of these pathways lead to the development of multiple human diseases, including neurological disorders, such as amyotrophic lateral sclerosis, Friedreich's ataxia, and Charcot-Marie-Tooth. A common hallmark in these disorders is mitochondrial dysfunction, associated with abnormal mitochondrial Ca 2+ handling that contributes to neurodegeneration. In this work, we highlight the importance of Ca 2+ signaling in mitochondria and how the mechanism of communication in MAMs is pivotal for mitochondrial maintenance and cell homeostasis. Lately, we outstand potential targets located in MAMs by addressing different therapeutic strategies focused on restoring mitochondrial Ca 2+ uptake as an emergent approach for neurological diseases.
Filiaciones:
Rodríguez LR:
Department of Physiology, Faculty of Medicine and Dentistry, Universitat de València-INCLIVA, 46010 Valencia, Spain
Associated Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 46010 Valencia, Spain
Lapeña-Luzón T:
Department of Physiology, Faculty of Medicine and Dentistry, Universitat de València-INCLIVA, 46010 Valencia, Spain
Associated Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 46010 Valencia, Spain
Benetó N:
Department of Physiology, Faculty of Medicine and Dentistry, Universitat de València-INCLIVA, 46010 Valencia, Spain
Associated Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 46010 Valencia, Spain
Beltran-Beltran V:
Department of Physiology, Faculty of Medicine and Dentistry, Universitat de València-INCLIVA, 46010 Valencia, Spain
:
Department of Physiology, Faculty of Medicine and Dentistry, Universitat de València-INCLIVA, 46010 Valencia, Spain
Associated Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 46010 Valencia, Spain
:
Department of Physiology, Faculty of Medicine and Dentistry, Universitat de València-INCLIVA, 46010 Valencia, Spain
Associated Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 46010 Valencia, Spain
Navarro JA:
Department of Genetics, Universitat de València-INCLIVA, 46100 Valencia, Spain
INCLIVA Biomedical Research Institute, 46010 Valencia, Spain
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