Mitochondria in Structural and Functional Cardiac Remodeling

Abstract

The heart must function continuously as it is responsible for both supplying oxygen and nutrients throughout the entire body, as well as for the transport of waste products to excretory organs. When facing either a physiological or pathological increase in cardiac demand, the heart undergoes structural and functional remodeling as a means of adapting to increased workload. These adaptive responses can include changes in gene expression, protein composition, and structure of sub-cellular organelles involved in energy production and metabolism. Mitochondria are essential for cardiac function, as they supply the ATP necessary to support continuous cycles of contraction and relaxation. In addition, mitochondria carry out other important processes, including synthesis of essential cellular components, calcium buffering, and initiation of cell death signals. Not surprisingly, mitochondrial dysfunction has been linked to several cardiovascular disorders, including hypertension, cardiac hypertrophy, ischemia/reperfusion and heart failure. The present chapter will discuss how changes in mitochondrial cristae structure, fusion/fission dynamics, fatty acid oxidation, ATP production, and the generation of reactive oxygen species might impact cardiac structure and function, particularly in the context of pathological hypertrophy and fibrotic response. In addition, the mechanistic role of mitochondria in autophagy and programmed cell death of cardiomyocytes will be addressed. Here we will also review strategies to improve mitochondrial function and discuss their cardioprotective potential.

Sirt3 Deficiency Shortens Life Span and Impairs Cardiac Mitochondrial Function Rescued by Opa1 Gene Transfer

“…It is worth mentioning that deacetylation of OPA1-but not of other mitochondrial proteins including SOD2-maintained in the long term in Sirt3 -/animals, corrected cardiac dysfunction and fibrosis, demonstrating this maneuvre's previously unanticipated potential for cardiac protection. Studies have shown that mitochondrial dysfunction in cardiomyocytes critically contributes to the development of age-associated cardiac fibrosis by impairing bioenergetics and reducing cell survival (1,28,49). Furthermore, based on the recent evidence that Complex I inhibition is sufficient to promote the development of fibrosis in the lung, it is tempting to infer that the normalization of Complex I activity through mutOpa1 gene transfer contributes to the amelioration of cardiac fibrosis (30).…”

New Insights in Cardiac Calcium Handling and Excitation-Contraction Coupling

“…Mitochondria play a strategic role in ensuring an adequate EC coupling (Miragoli and Cabassi 2017; Umanskaya et al 2014; Gambardella et al 2017; Torrealba et al 2017). Indeed, cardiac myocytes are critically dependent on constant and appropriate energy supply, alongside with a finely tuned Ca 2+ handling (Torrealba et al 2017; Sorriento et al 2017; Sheeran and Pepe 2017).…”

“…Indeed, cardiac myocytes are critically dependent on constant and appropriate energy supply, alongside with a finely tuned Ca 2+ handling (Torrealba et al 2017; Sorriento et al 2017; Sheeran and Pepe 2017). Mitochondria and SR are functionally and structurally associated and, at the point of interaction (mitochondrial associated membranes) Ca 2+ transits from SR to mitochondria (Min et al 2012; Bononi et al 2017).…”

Estimation of Adenosine Triphosphate Based Preparation Influence on Work Capacity during Modelling Of Intensive Continuous Physical Loads / Adenozintrifosfato ir mineralinių medžiagų mišinio įtaka eksperimentinių gyvūnų darbingumui atliekant didelės apimties ir intensyvumo krūvius

“…ATP also has antiarrhythmic, hypotensive, and anticonvulsant effects (Torrealba et al, 2017). It is also known that ATP stimulates the formation of cyclic AMP, which is a potent vasodilator that influences coronary arteries, in particular, whereas the reduced post-load in combination with improved myocardial circulation is accompanied by increased cardiac performance efficiency (Smolina et al, 2017).…”

“…Thus, today the interest in studying the ATP action in the body on the whole and under physical loads, in particular, is related to the fact that, during hypoxia, previously unknown properties of this substance as an endogenous intracellular regulator of cell functions and intercellular messenger tend to be manifested. It has been recently shown that protective effect of ATP on the body is mediated by both the restoration of macroergic substrate pool and the impact on the pathways of the receptor signal transmission, accompanied by changes in the expression of some genes (Liu et al, 2017;Torrealba et al, 2017), and increased activity of several enzymatic complexes, which determines cell metabolism on the whole. Within internal environment of a cell, the ATP molecule is in charge of the energy, including going through localized intracellular receptors to ATP, where it blocks the sensitive potassium channels, breaking down adenosine, moving outside, and influencing potassium channels (Smolina et al, 2017) through their activation.…”