Research Paper Volume 12, Issue 7 pp 6260—6275
Myotonic Dystrophy type 1 cells display impaired metabolism and mitochondrial dysfunction that are reversed by metformin
- 1 Neuroscience Area, Biodonostia Health Research Institute, San Sebastian, Spain
- 2 Cellular Oncology Group, Biodonostia Health Research Institute, San Sebastian, Spain
- 3 Neurology Department, Donostia University Hospital, OSAKIDETZA, San Sebastian, Spain
- 4 IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
- 5 CIBERfes, Carlos III Institute, Madrid, Spain
- 6 CIBERNED, Carlos III Institute, Madrid, Spain
- 7 Faculty of Medicine and Nursery, Department of Neurosciences, University of the Basque Country, San Sebastian, Spain
received: December 1, 2019 ; accepted: March 3, 2020 ; published: April 8, 2020 ;https://doi.org/10.18632/aging.103022
How to Cite
Copyright © 2020 García-Puga et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Myotonic dystrophy type 1 (DM1; MIM #160900) is an autosomal dominant disorder, clinically characterized by progressive muscular weakness and multisystem degeneration. The broad phenotypes observed in patients with DM1 resemble the appearance of a multisystem accelerated aging process. However, the molecular mechanisms underlying these phenotypes remain largely unknown. In this study, we characterized the impact of metabolism and mitochondria on fibroblasts and peripheral blood mononuclear cells (PBMCs) derived from patients with DM1 and healthy individuals. Our results revealed a decrease in oxidative phosphorylation system (OXPHOS) activity, oxygen consumption rate (OCR), ATP production, energy metabolism, and mitochondrial dynamics in DM1 fibroblasts, as well as increased accumulation of reactive oxygen species (ROS). PBMCs of DM1 patients also displayed reduced mitochondrial dynamics and energy metabolism. Moreover, treatment with metformin reversed the metabolic and mitochondrial defects as well as additional accelerated aging phenotypes, such as impaired proliferation, in DM1-derived fibroblasts. Our results identify impaired cell metabolism and mitochondrial dysfunction as important drivers of DM1 pathophysiology and, therefore, reveal the efficacy of metformin treatment in a pre-clinical setting.