Intramitochondrial inclusions caused by depletion of creatine in rat skeletal muscles

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.