Morphogenesis of the mitochondrial alterations in muscle diseases.

In this paper we present sequential morphologic changes produced in rat muscle mitochondria. Respiratory toxins such as crotoxin (rattle-snake venom) and 2,4-dinitrophenol (DNP-an uncoupler of oxidative phosphorylation) were injected in rat quadriceps muscle and the mitochondrial alterations were studied at various time intervals. The series of mitochondrial changes consisted of rounding and swelling of mitochondria, unfolding of the cristae as straight lines, formation of the concentric rings, appearance of paracrystalline inclusions, formation of multiple vesicles and finally vacuole formation. These changes were comparable to the range of mitochondrial alterations seen in the human material examined. Similarity of the time-related mitochondrial changes in the rat to the spectrum of changes observed in human muscle biopsies suggests that the mitochondrial alteration in the human muscle disorders is a stepwise process in which respiratory alterations and calcium ion may play a role.