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In recent years, the role of mitochondrial dynamics in neurodegenerative diseases has becoming increasingly important. More and more evidences have shown that in pathological conditions, abnormal mitochondrial divisions, especially Drp1-Fis1-mediated divisions, play an important role in the occurrence and development of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, glaucoma, and other neurodegenerative diseases. This review highlights several new mechanisms of physiological fission of mitochondria and the difference/connection of physiological/pathological mitochondrial fission. In addition, we described the relationship between abnormal mitochondrial dynamics and neurodegenerative diseases in detail and emphatically summarized its detection indicators in basic experiments, trying to provide references for further mechanism exploration and therapeutic targets.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 μM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg −1 ·d −1 , i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

Dystrophic calcinosis, which is the accumulation of insoluble calcified crystalline materials within tissues with normal circulating calcium and phosphorus levels, is a frequent finding in systemic sclerosis (SSc) and represents a major burden for patients. In SSc, calcinosis poses significant challenges in management due to the associated risk of severe complications such as infection, ulceration, pain, reduction in functional capacity and quality of life, and lack of standardized treatment choices. The exact pathogenesis of calcinosis is still unknown. There are multifaceted factors contributing to calcinosis development, including osteogenic differentiation of cells, imbalance between promoter and inhibitors of mineralization, local disturbance in calcium and phosphate levels, and extracellular matrix as a template for mineralization. Several pathophysiological changes observed in SSc such as ischemia, exacerbated production of excessive reactive oxygen species, inflammation, production of inflammatory cytokines, acroosteolysis, and increased extracellular matrix production may promote the development of calcinosis in SSc. Furthermore, mitochondrial dynamics, particularly fission function through the activity of dynamin-related protein-1, may have an effect on the dystrophic calcinosis process. In-depth investigations of cellular mechanisms and microenvironmental influences can offer valuable insights into the complex pathogenesis of calcinosis in SSc, providing potential targeting pathways for calcinosis treatment.

Microvascular changes in the pinna were studied in vivo and recorded photographically over a period of 12-18 months after irradiation of 4-month-old ${\\rm B}6{\\rm CF}_{1}$ mice. Radiation treatment consisted of total-body exposure to 240 rad fission neutrons either in a single dose or in 72 fractions of 3.3 rad each over 24 weeks. Neutrons with a mean energy of 0.8 MeV were supplied from the JANUS reactor. A fission neutron dose of 240 rad is below the acutely lethal range. At 20 months after treatment, after a series of in vivo observations of the microvasculature, animals were sacrificed for study of changes in vascular fine structure in the pinna. Blood vessels were selected from regions that had been identified on photomicrographs. After single or fractionated neutron exposures, the surviving functional blood vessels had relatively minor late ultrastructural changes in the endothelium. Many arterioles, however, showed extensive degenerative changes in the subendothelial intima (including the elastica) and marked necrosis of smooth muscle. Accumulations of fibrillar material and debris frequently occupied much of the media and replaced regions of smooth muscle lost by focal necrosis. Arteriolar degeneration and sclerosis appeared to be more extensive after fractionated treatments. Corresponding small veins or venules also showed smooth muscle degeneration and increased fibrosis, but changes were somewhat less severe than in arterioles. Capillary changes included a thickened basal lamina and increased fibrosis. Endothelial swelling and increased vacuolization were sometimes observed.

Experiments were performed to test the hypothesis that rats could be made permanently anemic by repeated mixed gamma-neutron irradiations and that once the maintenance of normal circulatory red cell concentration was lost, the administration of exogenous erythropoietin could not restore the production of red cells to normal levels. Rats were exposed to nine periodic doses of 150 rads of mixed gamma-neutron radiation or to four periodic doses of 300 rads. Hematocrits and erythrocyte counts obtained for 100 days or more after the final radiation exposure showed a significant reduction in erythrocyte production. This permanent anemia was not ameliorated by the treatment with five daily doses of either 5 units or 25 units of erythropoietin. These findings appear to strengthen the hypothesis that the permanent anemia is caused by a reduced capability for cellular proliferation due to accumulation of residual injury in stem cells.