Mitochondrial Pathologies and Their Neuromuscular Manifestations
Shamim I. Ahmad in Handbook of Mitochondrial Dysfunction, 2019
Early microscopic observations led to the idea that mitochondria were small, individual organelles randomly distributed within the cytoplasm. However, many teams have shown that mitochondria are highly structured, forming a complex network of interconnected tubules96,97. The mitochondrial network constitutes a dynamic system, constantly adapting to cellular requirements by changing its shape and position through processes of fission and fusion98. Indeed, the bioenergetic status of the cell is closely related to the structure of the mitochondrial network99. Insights acquired over the past decade show that mitochondrial dynamics plays a crucial role in several interdependent cellular processes such as bioenergetics, neuronal axonal transport, calcium homeostasis and apoptosis. In neurons, mitochondria are transported along the cytoskeleton of the axon, from the cell body to the periphery (anterograde transport) and from the periphery to the cell body (retrograde transport). Motor proteins of the kinesin (KIF) superfamily interact with mitochondria through the outer membrane proteins Miro1 and Miro2 and participate in anterograde transport. In contrast, cytoplasmic dynein motors mediate retrograde transport100,101. Another aspect of mitochondrial dynamics concerns fusion and fission mechanisms.
Structure and Function of Cartilage
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi in Articular Cartilage, 2017
Microtubules differ from actin and intermediate filaments in terms of both size and filament construction. Tubulin is a heterodimer composed of α/β monomers 55 kDa in size. It self-assembles into hollow 23 nm diameter “tubes” forming the microtubules, with an internal lumen diameter on the order of 15 nm. GTP binding is required for this assembly, and tubulin has GTPase activity, with GTP hydrolysis driving microtubule assembly. Microtubules also differ in their role in resisting force, acting to resist compression more than tension. The cilia and flagella (including the primary cilium) are composed of a microtubule arrangement described as 9 + 2, featuring an outer circle of nine microtubule doublets interconnected with dynein and with an inner arrangement of two microtubules. In addition to resisting compressive force, microtubules are also critically important in intracellular transport of organelles or vesicles through the actions of the dynein and kinesin motor proteins. The role of microtubules in intracellular transport is elegantly demonstrated in the assembly of the mitotic spindle, a structure that results in the intracellular movement and segregation of the replicated DNA into two daughter cells during mitosis.
Manipulating the Intracellular Trafficking of Nucleic Acids
Kenneth L. Brigham in Gene Therapy for Diseases of the Lung, 2020
Kinesin and cytoplasmic dynein are the principal ATPase microtubule-based motors involved in organelle transport (65-68). Each type of motor associates with membranous organelles and directs movement along the length of the microtubule. Dynein drives movement toward the minus end of the microtubule, yielding a net inward flow, whereas kinesin drives movement towards the plus end, generating movement toward the cell periphery (69). Dynein is responsible for movement of endosomal and lysosomal vesicles toward the cell nucleus, while kinesin has been implicated in maintaining the extended distribution of the endoplasmic reticulum, the shape of the Golgi complex, the extension of lysosomes, and trafficking of proteins from Golgi to endoplasmic reticulum (70-72).
Genetic aspects of idiopathic asthenozoospermia as a cause of male infertility
Published in Human Fertility, 2020
Zohreh Heidary, Kioomars Saliminejad, Majid Zaki-Dizaji, Hamid Reza Khorram Khorshid
DNAI1 (dynein axonemal intermediate chain 1), DNAH5 (dynein axonemal heavy chain 5) and DNAH11 (dynein axonemal heavy chain 11) genes encode three proteins belonging to the axonemal dynein cluster, particularly expressed in testis and trachea (Zuccarello, Ferlin, Cazzadore, et al., 2008). Dynein is a family of cytoskeletal motor proteins that move along microtubules in cells. There are two kinds of dynein: (i) cytoplasmic and (ii) axonemal. They convert the chemical energy stored in ATP to mechanical work (Roberts, Kon, Knight, Sutoh, & Burgess, 2013). Three missense mutations (R663C in DNAI1, E2666D in DNAH5 and I13040V in DNAH11) have been associated with AZS, with a frequency of 8.0%. These missense mutations cause substitution of amino acids, which are essential for the protein structure. These three proteins in the axonemal dynein cluster permanently attached to the A tubule of each outer microtubule doublet and transiently attached to the B tubule of the adjacent microtubule doublet, to generate a sliding motion (Zuccarello, Ferlin, Cazzadore, et al., 2008).
Molecular mechanisms governing axonal transport: a C. elegans perspective
Published in Journal of Neurogenetics, 2020
Amruta Vasudevan, Sandhya P. Koushika
Microtubule-dependent motor proteins responsible for most fast axonal transport in neurons largely belong to the Kinesin or Dynein superfamily (Morfini et al., 2012). Kinesins are ATPases that walk towards the plus ends of microtubules in a hand-over-hand motion, with each motor head taking 16 nm steps for every molecule of ATP hydrolysed (Gennerich & Vale, 2009). Cytoplasmic dynein, a member of the AAA family of ATPases, drives transport towards the minus ends of microtubules, using an inch-worm-like movement with occasional hand-over-hand mode of stepping (Bhabha, Johnson, Schroeder, & Vale, 2016; Gennerich & Vale, 2009). Studies on intracellular transport across diverse cell types have revealed common underlying principles governing microtubule-based transport, such as i) cargo-specific mechanisms of motor recruitment and transport, ii) interactions between multiple motors on the cargo surface, and iii) navigation of the cargo-motor complex through obstacles. Several of these principles have been found to apply to axonal transport. Neurons, being polarized cells with distinct axonal and dendritic compartments, additionally exhibit region-specific regulation of cargo transport. These principles are discussed below.
Flavanol-rich lychee fruit extract substantially reduces progressive cognitive and molecular deficits in a triple-transgenic animal model of Alzheimer disease
Published in Nutritional Neuroscience, 2021
Xiao Chen, Benhong Xu, Luling Nie, Kaiwu He, Li Zhou, Xinfeng Huang, Peter Spencer, Xifei Yang, Jianjun Liu
The ER protein category included 78 kDa glucose-regulated protein (GRP 78), an ER chaperone of the HSP70 family. GRP 78 was increased in 3×Tg-AD mice and decreased in Oligonol-treated animals. Pyruvate kinase muscle (KPYM), pyruvate dehydrogenase-related (ODPA), and NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (NDUS1) were found in the mitochondrial protein group. NDUS1, a component of mitochondrial Complex I, showed reduced expression in 3×Tg-AD mice and increased expression in Oligonol-treated animal groups. Both KPYM and OPDA participate in pyruvate metabolism. In the third category, Oligonol treatment counteracted the reduction of NDUS1 in the 3×Tg-AD group. The fourth category contained cytoplasmic dynein 1 intermediate chain 1 (DC1I1), dynamin 1, synapsin II and vimentin. Mean vimentin expression was increased in 3×Tg-AD mice and reduced in the Oligonol-treated 3×Tg-AD group. Administration of Oligonol also reduced the level of DC1I1. The synapsin II level was decreased in the 3×Tg-AD group and increased with Oligonol treatment. In summary, whereas the expression of selected proteins associated with the ER, mitochondria, proteasome, and synapse was perturbed in 3×Tg-AD mice, the perturbations were effectively reversed in animals treated with Oligonol.
Related Knowledge Centers
- Cytoskeleton
- Flagellum
- Intracellular Transport
- Kinesin
- Microtubule
- Motor Protein
- Cilium
- Mitosis
- Cell
- Adenosine Triphosphate