Crosstalk between Mitochondria and Cytoskeleton in Cardiac Cells

Abstract

Elucidation of the mitochondrial regulatory mechanisms for the understanding of muscle bioenergetics and the role of mitochondria is a fundamental problem in cellular physiology and pathophysiology. The cytoskeleton (microtubules, intermediate filaments, microfilaments) plays a central role in the maintenance of mitochondrial shape, location, and motility. In addition, numerous interactions between cytoskeletal proteins and mitochondria can actively participate in the regulation of mitochondrial respiration and oxidative phosphorylation. In cardiac and skeletal muscles, mitochondrial positions are tightly fixed, providing their regular arrangement and numerous interactions with other cellular structures such as sarcoplasmic reticulum and cytoskeleton. This can involve association of cytoskeletal proteins with voltage-dependent anion channel (VDAC), thereby, governing the permeability of the outer mitochondrial membrane (OMM) to metabolites, and regulating cell energy metabolism. Cardiomyocytes and myocardial fibers demonstrate regular arrangement of tubulin beta-II isoform entirely co-localized with mitochondria, in contrast to other isoforms of tubulin. This observation suggests the participation of tubulin beta-II in the regulation of OMM permeability through interaction with VDAC. The OMM permeability is also regulated by the specific isoform of cytolinker protein plectin. This review summarizes and discusses previous studies on the role of cytoskeletal proteins in the regulation of energy metabolism and mitochondrial function, adenosine triphosphate (ATP) production, and energy transfer.

Microtubule Organization in Striated Muscle Cells

“…It could be hypothesized that dominant MTOC function at the nuclear membrane improves mechanotransduction and allows timely and more precise modulation of gene expression in muscle cells. (4) Intracellular organization: Sarcomeres, mitochondria, and t-tubules (invaginations of the muscle cell membrane) exhibit a highly organized architecture [59,267,268]. Microtubule organization from the comparably large nuclear surface might be advantageous for the proper regular organization of the muscle cell interior.…”

“…(2) Positioning of organelles and intracellular organization [57][58][59][60][61][62][63][64][65]. (3) Mechanotransduction [66].…”

“…Furthermore, microtubules are involved in: (1) Formation of primary cilia [ 54 ] as well as motile cilia contributing to cell movement [ 55 ] or the generation of liquid flow [ 56 ]. (2) Positioning of organelles and intracellular organization [ 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. (3) Mechanotransduction [ 66 ].…”

VEGF-A in Cardiomyocytes and Heart Diseases

“…The interaction of these motor proteins guarantees the contraction of the muscle that allows blood to be pumped throughout the body [56][57][58]. Finally, CM contain a large number of mitochondria, which maintain high levels of ATP required by the cells to promote the contraction and relaxation of the heart muscle [59,60]. CM produce and secrete several mediators such as adiponectin [61], regenerating islet-derived protein 3-β [62], TNF-α, interleukin-1β (IL-1β), interferon γ [63], transforming growth factor β (TGF-β) [64], IL-6 and IL-11 [65,66].…”

Analysis of Reference Ranges of Total Serum Protein in Namibia: Clinical Implications

“…Proteins are also responsible for the transport of substances into the body, can act as enzymes, and play a role in fighting against infections (i.e., antibodies). Some proteins help in the development of structures in some organelles such as microfilaments and microtubules [9]. The direct method used in the determination of reference range of TSP is expensive, difficult to perform, often inaccurate, and non-reproducible.…”