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Mitochondrial Dysfunction in Huntington Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Md. Hafiz Uddin, Marufa Rumman, Tasnuva Sarowar
The lack of balance between mitochondrial fission and fusion negatively affects mitochondrial turnover. Autophagy, as previously referred, is an important intracellular mechanism that removes damaged organelles and misfolded/aggregated proteins to maintain cell homeostasis (Carvalho et al. 2015). Autophagy is characterized by the presence of autophagic vacuoles, autophagosomes (Kamat et al. 2014). An optimal level of autophagy is essential for recycling cellular organelles, which provides neuroprotection. However, increased autophagy is detrimental, causing neuronal degeneration (Kamat et al. 2014; Jing and Lim 2012; Wong and Cuervo 2010; Liu et al. 2009). Autophagy can be divided into two broad categories, namely, microautophagy and macroautophagy. In microautophagy, the lysosome directly engulfs intracellular smaller molecules and is independent of nutritional deprivation (Filosto et al. 2011). On the other hand, in macroautophagy, autophagosome is formed with intracellular larger molecules. This is then fused with the lysosome to generate autophagolysosome and undergoes subsequent degradation. Macroautophagy of mitochondria is termed as mitophagy [74,75].
Mitochondrial Dysfunction in Chronic Disease
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Christopher Newell, Heather Leduc-Pessah, Aneal Khan, Jane Shearer
Initially discovered in yeast, human homologues to the main components of both mitochondrial fission and fusion machinery have been identified along with their underlying mechanisms of action. In eukaryotes, mitochondrial fission is regulated by the proteins dynamin-related protein (DRP1), mitochondrial fission 1 protein (FIS1), mitochondrial fission factor (MFF), and mitochondrial dynamics proteins of 49 (MiD49) and 51 kDa (MiD51). Mitochondrial fusion is primarily regulated by the proteins mitofusin 1 (MFN1), mitofusin 2 (MFN2), and optic atrophy 1 (OPA1) (51). Fission involves the recruitment of the GTPase enzyme DRP1 from the cytosol to the OMM by MFF, FIS1, MiD49, and MiD51 (82). This recruitment stimulates DRP1 to form a helical assembly along the surface of the mitochondria and begins with constriction and culminates with the ultimate division of the mitochondria into two smaller, functional mitochondria (39). Research has also identified that the ER may have direct involvement in initiating fission by extending tubules which constrict the mitochondria prior to the recruitment of DRP1 (38). These ER tubules are extensions of the ER which wrap around neighbouring mitochondria and initiate a fission event.
Regulation of Antiviral Immunity by Mitochondrial Dynamics
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Mohsin Khan, Hasan Imam, Saiful Anam Mir
In eukaryotic cells, mitochondrial fission (or fragmentation) is a multistep process. It is categorized by the division of one mitochondrion into two daughter mitochondria. Recruitment of the dynamin related protein 1 (Drp1) plays a crucial role to initiate mitochondrial division (Frank et al., 2001). Drp1 has membrane remodeling property and it can localize to mitochondria and peroxisomes. Upon activation, it drives membrane scission in a GTP-dependent manner (Kraus and Ryan, 2017). Inhibition of Drp1 showed drastic elongation of both mitochondria and peroxisomes (Gandre-Babbe and van der Bliek, 2008; Koch et al., 2005; Lee et al., 2004). When mitochondrial fission occurs, Drp1 is recruited to the outer mitochondrial membrane (OMM) to form a ring like structure which causes the constriction of the OMM (Kraus and Ryan, 2017). Membrane scission starts through GTP hydrolysis, which marks a potential future site of mitochondrial scission (Kraus and Ryan, 2017). Fission has also been implicated in sorting the mitochondria with mutant mtDNA copies (Shitara et al., 2000). It is presumed that spontaneous depolarization during solitary stage can results into impairment of mitochondria (Twig et al., 2008; Twig and Shirihai, 2011) and sometimes, asymmetric fission can induce remarkable alteration in the mitochondrial membrane potential (ΔΨm) (Twig and Shirihai, 2011).
Impact of UCP2 depletion on heat stroke-induced mitochondrial function in human umbilical vein endothelial cells
Published in International Journal of Hyperthermia, 2022
Wei Huang, Liangfeng Mao, Weidang Xie, Sumin Cai, Qiaobing Huang, Yanan Liu, Zhongqing Chen
Mitochondria are essential organelles in mammalian cells, and play a central role in metabolism, cell death, and cellular senescence. Mitochondrial dysfunction, in the form of permeabilization of the inner and/or outer membranes of organelles, can eventually lead to cell apoptosis or necrosis [5,6]. Growing evidence suggests that mitochondrial dysfunction induces the loss of cellular homeostasis, which contributes to cell death during HS [7–9]. Mitochondrial function rests on the complex molecular machinery of mitochondrial dynamics-processes of fission and fusion [10]. A precise balance in mitochondrial dynamics is closely related to the maintenance of mitochondrial functions and responses to external stress [11]. Mitochondrial fission is driven by fission regulators, including mitochondrial fission factor (Mff), dynamin-related protein 1 (Drp1), and fission 1 (Fis1) [12]. In particular, the phosphorylation of Drp1 regulates its translocation to the mitochondrial membrane to induce mitochondrial fission [13,14]. Mitochondrial fusion is mediated by Mitofusin 1/2 (Mfn1/2) and optic atrophy 1 (OPA1) anchor proteins that maintain the fusion of the mitochondrial outer and inner membranes [15]. Therefore, researching the mechanism of mitochondrial homeostasis may provide an important breakthrough in HS therapy.
Sericin-mediated improvement of dysmorphic cardiac mitochondria from hypercholesterolaemia is associated with maintaining mitochondrial dynamics, energy production, and mitochondrial structure
Published in Pharmaceutical Biology, 2022
Kitiya Rujimongkon, Sumate Ampawong, Duangnate Isarangkul, Onrapak Reamtong, Pornanong Aramwit
Mitochondrial dynamics control mitochondrial function. Two key proteins representing the fission and fusion of mitochondria are DRP1 and OPA1, respectively. The mitochondrial fusion structure maintains the inner membrane structure and functions to protect cells from apoptosis, while mitochondrial fission is associated with apoptotic cell death (Parone and Martinou 2006). Related studies in a heart failure rat model have shown the relationship between dynamic protein expression and apoptosis. Reduced OPA1 but not DRP1 induces mitochondrial fragmentation, which is associated with apoptosis (Chen et al. 2009). In our study, the results demonstrated that cardiac mitochondria of hypercholesterolemic rats showed no alterations in DRP1 protein expression, whereas increased OPA1 expression was observed after sericin treatment. A caspase substrate in apoptosis, NDUFS1, was significantly reduced at the ghost stage of dysmorphic mitochondria. This evidence indicated that sericin maintained cardiac mitochondrial dynamics by increasing mitochondrial fusion and, consequently, prevented apoptosis. This dynamic action differed from that observed in liver mitochondria in a hypercholesterolaemia rat model; liver mitochondria show decreased DRP1 expression and increased OPA1 expression after sericin treatment (Ampawong et al. 2018), which implies that sericin treatment affects mitochondrial dynamics in different organs in distinct ways.
Amorphous silica nanoparticles caused lung injury through the induction of epithelial apoptosis via ROS/Ca2+/DRP1-mediated mitochondrial fission signaling
Published in Nanotoxicology, 2022
Yan Li, Yawen Zhu, Bosen Zhao, Qing Yao, Hailin Xu, Songqing Lv, Ji Wang, Zhiwei Sun, Yanbo Li, Caixia Guo
Then, in order to analyze the morphological alteration in mitochondria at the molecular level, mitochondrial fusion/fission proteins were detected. As depicted in Figure 5(C,D), the fission proteins, including DRP1 and FIS1, were up-regulated, whereas the fusion proteins (MFN1 and MFN2) were down-regulated in SiNPs group compared to control group (p < 0.05). No significant change in OPA1 expression was detected after SiNPs treatment. Of note, we determined the phosphorylation regulation of DRP1, apart from its total level. As a result, SiNPs increased p-DRP1s616 (a fission-promoting modification) while decreasing p-DRP1s637(a modification that can inactivate DRP1 activity), indicating DRP1 activation upon SiNPs exposure. In addition, the increased FIS1 may facilitate mitochondrial fission by recruiting DRP1 to mitochondria.