Preprint Article Version 1 This version is not peer-reviewed

Bezafibrate Improves Mitochondrial Fission and Function in DNM1L Deficient Patient Cells

Version 1 : Received: 6 August 2019 / Approved: 8 August 2019 / Online: 8 August 2019 (11:01:59 CEST)

How to cite: Douiev, L.; Sheffer, R.; Horvath, G.; Saada, A. Bezafibrate Improves Mitochondrial Fission and Function in DNM1L Deficient Patient Cells. Preprints 2019, 2019080101 (doi: 10.20944/preprints201908.0101.v1). Douiev, L.; Sheffer, R.; Horvath, G.; Saada, A. Bezafibrate Improves Mitochondrial Fission and Function in DNM1L Deficient Patient Cells. Preprints 2019, 2019080101 (doi: 10.20944/preprints201908.0101.v1).

Abstract

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 results 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, ATP production, oxygen consumption and s improved mitochondrial morphology in patient’s fibroblasts, albeit concomitantly causing a mild increase ROS production. 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 a possible treatment option for patients with certain DNM1L mutations.

Subject Areas

DNM1L; Drp1; mitochondrial disease; mitochondrial fission-fusion; Bezafibrate; fibroblast

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