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- W3150258889 abstract "Summary Cells rapidly lose their physiological phenotype upon isolation from their native microenvironment. Here, we investigated the role of the extracellular matrix (ECM) for mitochondrial morphology and Ca 2+ handling in adult mouse skeletal muscle fibres. Adult skeletal muscle fibres were isolated from mouse toe muscle either by collagenase-induced dissociation of the ECM or by mechanical dissection that leaves the proximate ECM intact. Experiments were generally performed four hours after cell isolation. At this time, the expression of genes encoding for structural proteins was lower in enzymatically dissociated than in mechanically dissected fibres. Mitochondrial appearance was grossly similar in the two groups, but 3D electron microscopy revealed shorter and less branched mitochondria in enzymatically dissociated than in mechanically dissected fibres. The increase in free cytosolic [Ca 2+ ] during repeated tetanic stimulation was similar in the two groups of fibres, but this was accompanied by an excessive mitochondrial Ca 2+ uptake only in enzymatically dissociated muscle fibres. The aberrant mitochondrial Ca 2+ uptake was partially prevented by the mitochondrial Ca 2+ uniporter inhibitor Ru360 and by cyclosporine A and NV556, which inhibit the mitochondrial matrix protein PPIF (also called cyclophilin D). Importantly, inhibition of PPIF with NV556 significantly improved survival of mice with mitochondrial myopathy in which muscle mitochondria take up excessive amounts of Ca 2+ also with intact ECM. In conclusion, skeletal muscle fibres isolated by collagenase-induced dissociation of the ECM display aberrant mitochondrial Ca 2+ uptake, which involves a PPIF-dependent mitochondrial Ca 2+ influx resembling that observed in mitochondrial myopathies." @default.
- W3150258889 created "2021-04-13" @default.
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- W3150258889 date "2021-03-30" @default.
- W3150258889 modified "2023-09-30" @default.
- W3150258889 title "Cytoskeleton-extracellular matrix interaction is required to maintain mitochondrial Ca2+ control in mouse skeletal muscle fibres" @default.
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- W3150258889 doi "https://doi.org/10.1101/2021.03.29.437546" @default.
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