Fragmentation of mitochondria is generally accepted as a typical reaction of cells to these stresses, and the fragmentation process has been reported to be caused by differential modulation of mitochondrial fission-fusion proteins 7.

Recently, the relationship between morphological changes in mitochondria and reactive oxygen species (ROS) has been studied extensively 6. However, the role of the tubular shape of mitochondria and the mechanisms regulating mitochondrial shape have not been elucidated. Although the relationship between mitochondrial shape and function is unclear, mitochondrial shapes are strictly determined by cells, organs, and species, and the elongation and fragmentation of mitochondria occur under different physiological or pathological conditions 5. Emerging evidence has shown that mitochondria are dynamic organelles that undergo continuous fission and fusion, the balance of which not only controls their morphology and number, but also regulates mitochondrial function and distribution 3, 4. Mitochondria can also form a network within the cell 1, 2. On average, mitochondria have a size of 0.75–3 µm 2, and their diameter and length vary considerably depending on the cell type or physiological state. Mitochondria are tubular-shaped, double membrane-bound organelles involved in various functions, including bioenergy production, apoptosis, autophagy, heme biosynthesis, oxygen sensing, and calcium homeostasis.

Our results suggested that loss of ΔΨm triggered collapse of mitochondrial structural support mechanisms. In contrast, most ring mitochondria did not have a true through hole rather, they had various indents, and 47% showed stomatocyte shapes with vase-shaped cavities, which is the most stable physical structure without any structural support if the long tubular shape shortens into a sphere. We found that most mitochondria changed from a tubular shape to a globular shape without fusion or fission and typically showed ring shapes within 10 min after CCCP exposure. We evaluated the early period of structural changes during the ΔΨm loss-induced transformation after carbonyl cyanide m-chlorophenyl hydrazine (CCCP) administration using a newly developed correlative microscopic method combined with fluorescence microscopic live imaging and volume electron microscopy. Loss of mitochondrial membrane potential (ΔΨm) triggers dramatic structural changes in mitochondria from a tubular to globular shape, referred to as mitochondrial fragmentation the resulting globular mitochondria are called swelled or ring/doughnut mitochondria.

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