Al-Sabri 2024 Sci Rep

Al-Sabri MH, Ammar N, Korzh S, Alsehli AM, Hosseini K, Fredriksson R, Mwinyi J, Williams MJ, Boukhatmi H, Schiöth HB (2024) Fluvastatin-induced myofibrillar damage is associated with elevated ROS, and impaired fatty acid oxidation, and is preceded by mitochondrial morphological changes. https://doi.org/10.1038/s41598-024-53446-w

» Sci Rep 14:3338. PMID: 38336990 Open Access

Al-Sabri Mohamed H, Ammar Nourhane, Korzh Stanislava, Alsehli Ahmed M, Hosseini Kimia, Fredriksson Robert, Mwinyi Jessica, Williams Michael J, Boukhatmi Hadi, Schioeth Helgi B (2024) Sci Rep

Abstract: Previously, we showed that fluvastatin treatment induces myofibrillar damage and mitochondrial phenotypes in the skeletal muscles of Drosophila. However, the sequential occurrence of mitochondrial phenotypes and myofibril damage remains elusive. To address this, we treated flies with fluvastatin for two and five days and examined their thorax flight muscles using confocal microscopy. In the two-day fluvastatin group, compared to the control, thorax flight muscles exhibited mitochondrial morphological changes, including fragmentation, rounding up and reduced content, while myofibrils remained organized in parallel. In the five-day fluvastatin treatment, not only did mitochondrial morphological changes become more pronounced, but myofibrils became severely disorganized with significantly increased thickness and spacing, along with myofilament abnormalities, suggesting myofibril damage. These findings suggest that fluvastatin-induced mitochondrial changes precede myofibril damage. Moreover, in the five-day fluvastatin group, the mitochondria demonstrated elevated H₂O₂ and impaired fatty acid oxidation compared to the control group, indicating potential mitochondrial dysfunction. Surprisingly, knocking down Hmgcr (Drosophila homolog of HMGCR) showed normal mitochondrial respiration in all parameters compared to controls or five-day fluvastatin treatment, which suggests that fluvastatin-induced mitochondrial dysfunction might be independent of Hmgcr inhibition. These results provide insights into the sequential occurrence of mitochondria and myofibril damage in statin-induced myopathy for future studies.

• Bioblast editor: Plangger M • O2k-Network Lab: LV Riga Liepins E

Labels: MiParea: Respiration, Pharmacology;toxicology 

Organism: Drosophila 

Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, Gp, NS, ROX  HRR: Oxygraph-2k, O2k-Fluorometer 

2023-02, AmR