Crosstalk between Mitochondria and Cytoskeleton in Cardiac Cells

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.

Cells are highly organized units with multifaceted functional and structural interactions between various subcellular systems. A large number of studies provides strong evidence that elucidating individual organelles alone is not sufficient, and only systemic approaches must be applied for understanding intracellular signaling pathways and crosstalk between subcellular organelles. This may involve a “systems biology” approach and combinations of several most modern technologies such as genetic manipulations, live cell imaging, mathematical modelling, etc.

Many structural and functional interactions were found to be involved in the integration of mitochondria with other cellular systems like the SR and cytoskeleton, connecting mitochondrial function, dynamics, and regulation with the entire cell physiology, in particular in the most energy consuming organ, the heart.

The detailed characterization of molecular mechanisms implicated in mitochondrial–cytoskeleton interactions under normal and pathological conditions can be helpful for the development of new therapeutic approaches.

many structural and functional aspects of mitochondria–cytoskeletal proteins interactions, as well as detailed molecular mechanisms of their formation, are not yet known, and the interactions of tubulin beta-II or plectin 1b with mitochondria (mitochondrial VDAC) have to be shown more directly, using the most modern methodologies