**1. Introduction**

The heart is the most metabolically active organ in the body and highly depends on oxidative energy generation in mitochondria to supply the large amount of adenosine triphosphate (ATP) required for its continuous contractile activity. In addition, cardiac mitochondria also serve other cellular functions such as generating and regulating reactive oxygen species (ROS), buffering cytosolic calcium ions (Ca2+), and regulating cellular apoptosis through the mitochondrial permeability transition pore (mPTP).

Heart disease is the leading cause of mortality worldwide. Although the study of mitochondrial function in the human heart faces many obstacles, the role of mitochondria in cardiac diseases has been elucidated from the studies with animal models. Increasing evidences have shown that abnormalities in the mitochondrial structure and function are tightly associated with development of various cardiovascular diseases, which prompted new therapies to treat and prevent heart disease by aiming at metabolic modulation.

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

Mitochondrial abnormalities include impaired mitochondrial electron transport chain (ETC) activity, increased formation of ROS, shifted metabolic substrate utilization, aberrant mitochondrial dynamics, and altered ion homeostasis. Some of the mitochondrial abnormalities may have a genetic basis due to the changes of mitochondrial DNA (mtDNA) or the mutation of specific nuclear DNA (nDNA), while other abnormalities are due to environmental cardiotoxic insult or uncharacterized reasons. Although many specific mitochondrial targets have proven to be promising therapeutic strategies in experimental studies, most of them are pending for validation through clinical trials. Better understanding the molecular mechanism of mitochondria in cardiac pathology is important to provide diagnosis and treatment of mitochondrial-based cardiac diseases.

from creatine by mitochondrial creatine kinase (mitoCK) using ATP from the closely associ-

Mitochondria and Heart Disease

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http://dx.doi.org/10.5772/intechopen.72611

Additionally, the heart is a well vascularized organ, allowing for delivery of freshly oxygenated blood and quick removal of the waste products of metabolism. This constant supply of oxygen is important for OXPHOS to take place, as oxygen serves as the final electron acceptor in the ETC. Understanding the factors involved in the development and function of mitochondrial energy production pathways is increasingly important due to the many diseases

Energy production within the cardiomyocytes of the heart is influenced by genetic factors as well as environmental factors. nDNA and mtDNA affect the enzymes and their cofactors as well as the availability of substrates to the mitochondria from their surroundings, which further influence OXPHOS. Cardiac tissue has specific gene regulations to meet its physiological and developmental needs. For example, the ATP synthase β-subunit is expressed at higher levels in cardiomyocyte-differentiated cells compared to control cells [3], and some isoforms of enzymes, e.g., cardiac specific isoforms of cytochrome c oxidase subunits VIa, VIIa, and

Besides the expression and function of the main proteins associated with the OXPHOS, the component of the ETC complexes I-IV and ATP synthase (complex V), many other molecules have been found to be involved in the regulation of the mitochondrial energy production through posttranslational modification. For example, proteins within the mitochondrial complexes can be nitrosylated (the addition of an NO group) or *O*-GlcNAcylated (the addition of *O*-linked β-*N*-acetylglucosamine (*O*-GlcNAc)) [5, 6]. These protein modifications modulate the activity of the complexes and hence change the efficiency of the mitochondria to meet the physiological function of the heart. In addition, our recent studies have also found a specific cell survival-promoting signaling that plays an important regulatory role in promoting ETC efficiency in cardiomyocytes, remarkably under the cardiac stress [7–9]. In particular, we found that this signaling pathway, which includes the heat shock protein 22(Hsp22), AKT, and valosin-containing protein (VCP), promotes ETC efficiency in cardiomyocyte through the

Ca2+ concentration is highly regulated in the myocardium and is responsible for the induction and intensity of contraction in the myocytes [10]. Mitochondria are able to modulate the Ca2+ concentration in the cardiomyocyte, which plays an important role in the cardiac function [11]. Mitochondria can directly decrease the Ca2+ concentration in the cytosol of the cell by importing Ca2+ via the mitochondrial Ca2+ uniporter. Reciprocally, they can also increase the Ca2+ concentration in the cytosol by expelling calcium stored within the mitochondria through

for physiological responses to cytosolic calcium signals and the loading of Ca2+ in the mitochondrial matrix. Mitochondria partake in the cardiac excitation-contraction coupling (ECC) by storing Ca2+, responding to cytosolic calcium signals and generating the ATP required for cardiac contraction. Ca2+ influx via L-type Ca2+ channels triggers further release of Ca2+ from

/Ca2+ exchangers [12]. This elaborate system of channels and transporters allows

ated adenine nucleotide translocase (ANT) and mitochondrial ATP synthase [2].

associated with defects in this machinery.

VIII, are differentially expressed across tissues [4].

*2.1.2. Modulation of calcium signaling*

Na+

/Ca2+ or H+

increase of mitochondrial inducible nitric oxide synthase (iNOS) [7–9].

In order to better understand the role that the mitochondrion plays in the heart, we provide in this chapter a brief background describing the regulation and function of mitochondria during normal cardiac development and aging as well as the pathological mechanisms involved in cardiac diseases. We also address the mitochondrial abnormalities–based diagnosis and therapeutic options available in heart disease.
