Mitochondria as target of endocrine-disrupting chemicals: implications for type 2 diabetes

Abstract

Type 2 diabetes is a chronic, heterogeneous syndrome characterized by insulin resistance and pancreatic β-cell dysfunction or death. Among several environmental factors contributing to type 2 diabetes development, endocrine-disrupting chemicals (EDCs) have been receiving special attention. These chemicals include a wide variety of pollutants, from components of plastic to pesticides, with the ability to modulate endocrine system function. EDCs can affect multiple cellular processes, including some related to energy production and utilization, leading to alterations in energy homeostasis. Mitochondria are primarily implicated in cellular energy conversion, although they also participate in other processes, such as hormone secretion and apoptosis. In fact, due to mitochondria involvement in so many crucial cellular processes in metabolic relevant tissues, mitochondrial dysfunction has been linked to different metabolic diseases, including insulin resistance and type 2 diabetes. Herein, we review the main mechanisms whereby metabolism-disrupting chemical (MDC), a subclass of EDCs that disturbs energy homeostasis, cause mitochondrial dysfunction, thus contributing to the establishment of insulin resistance and type 2 diabetes. We conclude that MDC-induced mitochondrial dysfunction, which is mainly characterized by perturbations in mitochondrial bioenergetics, biogenesis, and dynamics, excessive reactive oxygen species production, and activation of the mitochondrial pathway of apoptosis, seems to be a relevant mechanism linking MDCs to type 2 diabetes development.

The antiandrogenic vinclozolin induces differentiation delay of germ cells and changes in energy metabolism in 3D cultures of fetal ovaries

“…Androgen precursors may contribute to the synthesis of estrogens, mediated by aromatase (CYP19) 62 . Estrogens are involved in mitochondrial metabolism and function 63 Mitochondria is a prevalent target of EDCs 64 Alteration of energy metabolism by mitochondrial dysfunctions has been associated to the exposure to several EDCs 65,66 . About 800 EDCs are considered as disrupters of mitochondrial membrane potential 67 .…”

Relationship between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues

“…The mitochondrial genome encodes proteins that are part of the ETC and are essential for ATP production, and it is well established that mutations in the mitochondrial genome predispose subjects to diabetes [12,14,15]. For instance, a recent prospective study carried out in individuals with mitochondrial disease found a higher incidence of endocrine disorders such as diabetes mellitus [13].…”

Role of Endocrine-Disrupting Chemicals in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: A Comprehensive Review

“…In light of this, EDCs may play a potential role in mitochondrial dysfunction, and their link with NAFLD has been proposed. Studies show that EDCs’ effects on mitochondrial bioenergetics, dynamics, biogenesis, and antioxidant capacity are implicated in the development of IR, T2DM, and MetS [ 104 , 105 ]. With this broad view, it has been shown that atrazine [ 106 ] and BPA [ 107 ] exert direct mitochondrial toxicity in HepG2 cells through the reduction in mainspring genes involved in mitochondrial function such as mitochondrial transcription factor A ( TFAM ) and sirtuin 1 ( SIRT1 ) and MRC interruption, which leads to a decrease in oxidative phosphorylation (OXPHOS) and ATP production.…”