Gemmink 2023 Mol Metab
|Gemmink A, Daemen S, Wefers J, Hansen J, van Moorsel D, Astuti P, Jorgensen JA, Kornips E, Schaart G, Hoeks J, Schrauwen P, Hesselink MKC (2023) Twenty-four hour rhythmicity in mitochondrial network connectivity and mitochondrial respiration; a study in human skeletal muscle biopsies of young lean and older individuals with obesity. https://doi.org/10.1016/j.molmet.2023.101727|
» Mol Metab 72:101727. PMID: 37062525 Open Access
Gemmink Anne, Daemen Sabine, Wefers Jakob, Hansen Jan, van Moorsel Dirk, Astuti Puji, Jorgensen Johanna A, Kornips Esther, Schaart Gert, Hoeks Joris, Schrauwen Patrick, Hesselink Matthijs KC (2023) Mol Metab
Abstract: Mitochondrial network dynamics may play role in metabolic homeostasis. Whether mitochondrial network dynamics are involved in adaptations to day-night fluctuations in energy supply and demand is unclear. Here we visualized and quantified the mitochondrial network morphology in human skeletal muscle of young healthy lean and older individuals with obesity over the course of 24 h.
Muscle biopsies taken at 5 timepoints over a 24-hour period obtained from young healthy lean and older metabolically impaired obese males were analyzed for mitochondrial network integrity with confocal laser scanning microscopy. Variation of level of fragmentation over the course of the day were aligned with variation of mitochondrial respiration over the day.
Young healthy lean individuals displayed a day-night rhythmicity in mitochondrial network morphology, which aligned with the day-night rhythmicity of mitochondrial respiratory capacity, with a more fused network coinciding with higher mitochondrial respiratory capacity. In the older individuals with obesity, the mitochondrial network was more fragmented overall compared to young healthy lean individuals and completely lacked 24 h rhythmicity, which was also true for the mitochondrial respiratory capacity.
Our data shows a paralleled rhythmicity between mitochondrial network morphology and mitochondrial oxidative capacity, which oscillates over the course of a mimicked real-life day in human skeletal muscle of young, healthy lean individuals. In older individuals with obesity, the lack of a 24-hour rhythmicity in mitochondrial network connectivity was also aligned with a lack in respiratory capacity. This suggests that 24-hour rhythmicity in mitochondrial network connectivity is a determinant of rhythmicity in mitochondrial respiratory capacity. Thus, restoring mitochondrial network integrity may promote mitochondrial respiratory capacity and hence contribute to blunting the metabolic aberrations in individuals with a disturbed 24-hour rhythmicity in metabolism, like older individuals with obesity. • Keywords: Day-night rhythm, Mitochondrial function, Mitochondrial network integrity, Skeletal muscle • Bioblast editor: Plangger M • O2k-Network Lab: NL Maastricht Schrauwen P
Labels: MiParea: Respiration, Comparative MiP;environmental MiP
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, NS HRR: Oxygraph-2k