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Effect of creatine depletion by beta-guanidinopropionic acid (beta-GPA) feeding on mitochondrial morphology was studied in rats. Following beta-GPA feeding for 9 weeks, intramitochondrial inclusions running parallel to the long axis of mitochondrion were observed in skeletal muscles. A bundle of inclusions consisted of four parallel arrays containing electron-dense materials. Two outer arrays were continuous with cristal membranes and two inner arrays were chains of fine particles. Mitochondria with such inclusions were elongated probably in only a certain direction even though it was suggested that the layers of cristae were straightened two-dimensionally. Longer mitochondria ran parallel to the muscle fibers. It was also suggested that chronic stimulation of mitochondrial biogenesis by depletion of high energy phosphates may induce such inclusions within mitochondria.

Intramitochondrial inclusions caused by depletion of creatine in rat skeletal muscles.