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Glucolipotoxicity-induced oxidative stress and mitochondrial dysfunction of pancreatic β-cells are one of the
mechanisms that have been related to the low insulin secretion and cell death during diabetes development. In early or
non-chronic stages, the pancreatic β-cells respond to hyperglycemia or hyperlipidemia, stimulating insulin secretion.
However, the chronic effect of both leads to the establishment of glucolipotoxicity which induces constant
overstimulation of pancreatic β-cells, a condition that leads to cell death by apoptosis. The mechanism described, at this
moment, is the accelerated mitochondrial dysfunction triggered by the high production of reactive oxygen species (ROS)
due to excess nutrients. At first, mitochondria respond to over-nutrition accelerating oxygen consumption and
consequently increasing the ATP synthesis. A permanent increase of ATP/ADP ratio leads to a constant inhibition of
K+
ATP-channel and therefore a continuous insulin secretion accompanied by an increase in ROS. Finally, ROS
accumulation compromises mitochondrial function due to the uncontrolled oxidation of proteins, lipids, and DNA
generating functional alterations such as a drop of membrane potential, deregulation of mitochondrial dynamics, low rate
of ATP synthesis and consequently the cell death. This review aims to describe the effect of glucolipotoxicity-induced
oxidative stress and its relationship with mitochondrial dysfunction in β-cell during type 2 diabetes development.
Mitochondria modify their function and morphology to satisfice the bioenergetic demand of the cells. Cancer cells take advantage of these features to sustain their metabolic, proliferative, metastatic, and survival necessities. Therefore, the understanding of mitochondrial morphologic changes of the different grades of Triple-Negative Breast Cancer (TNBC) could be relevant for the design of novel treatments. Consequently, this research aimed to explore the mitochondria morphology and gene expression of some proteins related to mitochondrial dynamics as well as proteins related to oxidative and non-oxidative metabolism of metastatic and non-metastatic TNBC. We found that mitochondrial-morphology and metabolism are different between metastatic and non-metastatic TNBC. Metastatic TNBC showed overexpression of genes related to mitochondrial dynamics, fatty acids, and glycolytic metabolism. These features were accompanied by a fused mitochondrial morphology. In contrast, the non-metastatic TNBC presented a stress-associated mitochondrial morphology, hyperfragmented mitochondria accompanied by upregulated expression of mitochondrial biogenesis-related genes, both characteristics related to the higher ROS production observed in this cell line. These differences found between metastatic and non-metastatic TNBC will allow a better understanding of the metastasis process and the improvement of the development of a specific and personalized TNBC therapy.
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