Bezafibrate Improves Mitochondrial Fission and Function in DNM1L-Deficient Patient Cells
1
Department of Genetic and Metabolic Diseases and Jacques Roboh Department of Genetic Research, Hadassah Medical Center, Jerusalem 9112001, Israel
2
Division of Biochemical Diseases, Department of Pediatrics, University of British Columbia, Vancouver, BC BC V6H 3V4, Canada
3
Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(2), 301; https://doi.org/10.3390/cells9020301
Received: 2 January 2020
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Revised: 19 January 2020
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Accepted: 21 January 2020
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Published: 27 January 2020
(This article belongs to the Special Issue Mitochondrial Dynamics: Fusion and Fission)
Mitochondria are involved in many cellular processes and their main role is cellular energy production. They constantly undergo fission and fusion, and these counteracting processes are under strict balance. The cytosolic dynamin-related protein 1, Drp1, or dynamin-1-like protein (DNM1L) mediates mitochondrial and peroxisomal division. Defects in the DNM1L gene result in a complex neurodevelopmental disorder with heterogeneous symptoms affecting multiple organ systems. Currently there is no curative treatment available for this condition. We have previously described a patient with a de novo heterozygous c.1084G>A (p.G362S) DNM1L mutation and studied the effects of a small molecule, bezafibrate, on mitochondrial functions in this patient’s fibroblasts compared to controls. Bezafibrate normalized growth on glucose-free medium, as well as ATP production and oxygen consumption. It improved mitochondrial morphology in the patient’s fibroblasts, although causing a mild increase in ROS production at the same time. A human foreskin fibroblast cell line overexpressing the p.G362S mutation showed aberrant mitochondrial morphology, which normalized in the presence of bezafibrate. Further studies would be needed to show the consistency of the response to bezafibrate, possibly using fibroblasts from patients with different mutations in DNM1L, and this treatment should be confirmed in clinical trials. However, taking into account the favorable effects in our study, we suggest that bezafibrate could be offered as a treatment option for patients with certain DNM1L mutations.
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Keywords:
DNM1L; Drp1; mitochondrial disease; mitochondrial fission-fusion; bezafibrate; fibroblast
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MDPI and ACS Style
Douiev, L.; Sheffer, R.; Horvath, G.; Saada, A. Bezafibrate Improves Mitochondrial Fission and Function in DNM1L-Deficient Patient Cells. Cells 2020, 9, 301. https://doi.org/10.3390/cells9020301
AMA Style
Douiev L, Sheffer R, Horvath G, Saada A. Bezafibrate Improves Mitochondrial Fission and Function in DNM1L-Deficient Patient Cells. Cells. 2020; 9(2):301. https://doi.org/10.3390/cells9020301
Chicago/Turabian StyleDouiev, Liza, Ruth Sheffer, Gabriella Horvath, and Ann Saada. 2020. "Bezafibrate Improves Mitochondrial Fission and Function in DNM1L-Deficient Patient Cells" Cells 9, no. 2: 301. https://doi.org/10.3390/cells9020301
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