Mitochondria and Embryo Viability
Carlos Simón, Carmen Rubio in Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Mitochondria play a critical role in the generation of metabolic energy in eukaryotic cells, using oxidative phosphorylation to derive energy (ATP) from carbohydrates and fatty acids. Mitochondria contain their own DNA, which encodes tRNAs, rRNAs, and some mitochondrial proteins (1). Ranging in size from 0.5 to 1.0 μm in diameter (2), these unique organelles have a double-membrane system consisting of inner and outer membranes separated by an intermembrane space (1). The outer mitochondrial membrane encloses the matrix (internal space) and contains a large number of proteins that form channels allowing small molecules to pass. The inner mitochondrial membrane, which is folded into structures (cristae) that increase the surface area, is less permeable, blocking the movement of ions and other small molecules. Both the inner and outer membranes contain specific transport proteins that can move molecules by a passive or active transport (2) (Figure 15.1).
The Role of Nanoparticles in Cancer Therapy through Apoptosis Induction
Hala Gali-Muhtasib, Racha Chouaib in Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
The superfamily of BCl-2 family proteins located in the mitochondrial membrane determines cell fate decisions (i.e., cell survival or death) by controlling MOMP. Members of this family are classified into two groups, including pro-apoptotic or anti-apoptotic proteins, and are in the forms of homodimers or heterodimers. The pro-apoptotic proteins are further classified as multi-domain members, such as BCL-2 homology (BH) domain proteins such as BAX, BCLXs, and BAK, or single domain members, including BH3-only proteins BID, BIM, BAD, PUMA (p53 upregulated controller of apoptosis), and NOXA. The anti-apoptotic members contain multi-BH domain and include BCL-2, BCL-XL and MCL-1. Owing to the crucial role of BCL-2 family proteins, especially BH3-only proteins, in regulating and promoting apoptosis, they could be a potential target for therapeutic options [30]. Under normal physiological conditions, there is a balance between pro-apoptotic (BAX, BID, BAK or BAD) and anti-apoptotic (BCL-XL and BCL-2) members of the BCL-2 family. This balance can be disrupted by an internal stimulus, leading to an increase in the pro-apoptotic BCL-2 family members or the decrease in the anti-apoptotic BCL-2 family proteins. In most conditions, pro-apoptotic homodimers in the outer membrane of the mitochondrion are formed to make the mitochondrial membrane permeable to release cytochrome c and SMAC which, in turn, trigger the activation of apoptosis cascade [31].
Mitochondria in Huntington’s Disease
Abhai Kumar, Debasis Bagchi in Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Mitochondria, OXPHOS, and HD: Mitochondria play a crucial role in generating and delivering cellular energy currency, that is, ATP. Mitochondria have an outer mitochondrial membrane (OMM) and an inner mitochondrial membrane (IMM), which has a larger surface area and is folded to fit inside OMM creating cristae. Cristae are the seat of mitochondrial oxidative phosphorylation (OXPHOS) machinery, namely, electron transport chain (ETC) complexes I–IV, two electron carriers, and a specialized ATP synthesizing enzyme called ATP synthase. The space between the two membranes of mitochondria is called intermembrane space and the space constrained by the IMM is called matrix, which is filled with a gel-like substance. The matrix contains the mtDNA and the enzymes of the tricarboxylic acid (TCA) cycle (also known as the citric acid cycle or Krebs cycle). Due to the high energy demand and limited regenerative capability of neurons, mitochondrial dysfunction (broadly including individual enzyme complex deficiencies or fusion-fission abnormalities or disrupted movement along the cytoskeletal elements) is especially debilitating for these specialized cells.
Targeting mitochondria in dermatological therapy: beyond oxidative damage and skin aging
Published in Expert Opinion on Therapeutic Targets, 2022
Tongyu C Wikramanayake, Jérémy Chéret, Alec Sevilla, Mark Birch-Machin, Ralf Paus
Before going into details, it may be useful to recapitulate some essentials of mitochondrial biology. Reminiscent of their endosymbiont past, mitochondria are surrounded by two phospholipidic membranes, the outer mitochondrial membrane (OMM) and the inner mitochondrial membrane (IMM), which divide the organelle into two compartments, the matrix and the intermembrane space (IMS) [212] (see Figure 2 for details). Mitochondria contain their own DNA (mtDNA) and translation system. The location of mtDNA in the matrix, in close proximity to the ETC, a major source of reactive oxygen species (ROS), makes it particularly vulnerable to oxidation, resulting in mtDNA mutations that could contribute to the pathogenesis of cancer, diabetes and aging [213]. Mutations in mtDNA are functionally recessive – a biochemical phenotype is only observed when the levels of mutated mtDNA reach a critical threshold, and the proportion of mutated versus wild-type mtDNA has a strong impact on the severity of the pathological phenotypes. Coenzyme Q (CoQ10), a ROS scavenger, and mitochondrial sirtuins (SIRT3 and SIRT4) have been implicated in maintaining mitochondrial health [109,214].
miR-761-hepcidin/Gpx4 pathway contribute to unexplained liver dysfunction in polycystic ovary syndrome by regulating liver iron overload and ferroptosis
Published in Gynecological Endocrinology, 2023
Ruoheng Zheng, Chuanping Lin, Yuchan Mao, Fan Jin
Ferroptosis is a novel identified Fe-dependent form of cell death in mammalian cells. The key processes of ferroptosis are the accumulation of intracellular Fe and the requirement of lipid peroxidation. The ferroptotic cells show condensed mitochondrial membrane densities, vanishing of mitochondria crista and rupture of outer mitochondrial membrane at the ultrastructural level [23]. Ferroptosis has recently been intensively investigated for putative involvement in numerous pathophysiological process [24,25]. However, its role in liver damage of PCOS patients remains unclear. Therefore, we hypothesize that downregulated hepcidin in PCOS patients leads to hepatic Fe deposition, which in turn activates ferroptosis, causing NAFLD independent liver damage. Besides, microRNA may exert regulatory function on hepcidin and further participate in PCOS associated liver damage. By using PCOS mice model and cell line, we tried to reveal the underlying mechanism and provide novel ideas and targets in prevention and treatment of PCOS patients with liver damage.
The inverse relation between mitochondrial transmembrane potential and proteins α-helix in neuronal-like cells under static magnetic field and the role of VDAC
Published in Electromagnetic Biology and Medicine, 2020
Emanuele Calabrò, Salvatore Magazù, Monica Currò, Riccardo Ientile
Also, mitochondria and mitochondrial membrane have an important role in cellular function, providing energy in the cell by the adenosine triphosphate (ATP) synthesis, in order to drive the most important functions in cells. Outer and inner mitochondrial membrane separate mitochondria from the cytoplasm (Kühlbrandt 2015). In particular, some membrane protein located in the outer mitochondrial membrane, named voltage-dependent anion channel (VDAC), has the role to be a primary filter for mitochondria, importing large molecules and selecting ions' passage based on their size (Colombini 2012, 2016; Mertins et al. 2014). In the open state of VDAC, there is a preference for anions over cations which can be induced by the presence of a fixed charge distribution on the wall of the channel (Lee et al. 2011). In contrast, a preference for the passage of cations should occur in the closed state. Indeed, in this state, VDAC is not completely closed having a 30–40% drop in effective pore diameter (Colombini et al. 1996) so that pore constriction could favor cations to be transported across VDAC due to their smaller dimensions (Reina et al. 2013), and the channel is poorly permeable to large metabolites such as succinate, phosphate, citrate and ATP (Bowen et al. 1985; Rostovtseva and Colombini 1997).
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