Functional Role of Mitochondria in Arrhythmogenesis

Gambardella, Jessica; Sorriento, Daniela; Ciccarelli, Michele; Giudice, Carmine Del; Fiordelisi, Antonella; Napolitano, Luigi; Trimarco, Bruno; Iaccarino, Guido; Santulli, Gaetano

doi:10.1007/978-3-319-55330-6_10

Cited by 49 publications

(51 citation statements)

References 61 publications

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“…ATP production is established via the mitochondrial membrane potential ( m = −180 mV). The m creates a proton motive force which provides energy necessary to phosphorylate adenosine diphosphate (ADP) to ATP (Gambardella et al, 2017). This mechanism is also one of the main sources for reactive oxygen species (ROS) in the cell (Yang et al, 2014).…”

Section: Cardiac Mitochondrial (Patho)physiologymentioning

confidence: 99%

“…Under physiological conditions, m is tightly controlled and ATP production is in equilibrium with the energy demands of the cell. In response to pathological stimuli, such as ischemia or structural injury, alterations in m diminish the cellular ATP level and increase ROS production (Gambardella et al, 2017). If ROS production exceeds the detoxifying (scavenging) capacity of the cell, it creates oxidative stress (Gambardella et al, 2017).…”

Section: Cardiac Mitochondrial (Patho)physiologymentioning

confidence: 99%

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Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms

et al. 2019

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Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease, associated with ventricular arrhythmias, fibrofatty replacement of the myocardial mass and an increased risk of sudden cardiac death (SCD). Malignant ventricular arrhythmias and SCD largely occur in the pre-clinical phase of the disease, before overt structural changes occur. To prevent or interfere with ACM disease progression, more insight in mechanisms related to electrical instability are needed. Currently, numerous studies are focused on the link between cardiac arrhythmias and metabolic disease. In line with that, a potential role of mitochondrial dysfunction in ACM pathology is unclear and mitochondrial biology in the ACM heart remains understudied. In this review, we explore mitochondrial dysfunction in relation to arrhythmogenesis, and postulate a link to typical hallmarks of ACM. Mitochondrial dysfunction depletes adenosine triphosphate (ATP) production and increases levels of reactive oxygen species in the heart. Both metabolic changes affect cardiac ion channel gating, electrical conduction, intracellular calcium handling, and fibrosis formation; all well-known aspects of ACM pathophysiology. ATP-mediated structural remodeling, apoptosis, and mitochondria-related alterations have already been shown in models of PKP2 dysfunction. Yet, the limited amount of experimental evidence in ACM models makes it difficult to determine whether mitochondrial dysfunction indeed precedes and/or accompanies ACM pathogenesis. Nevertheless, current experimental ACM models can be very useful in unraveling ACM-related mitochondrial biology and in testing potential therapeutic interventions.

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Section: Cardiac Mitochondrial (Patho)physiologymentioning

confidence: 99%

Section: Cardiac Mitochondrial (Patho)physiologymentioning

confidence: 99%

Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms

et al. 2019

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“…Alterations in ATP and ROS levels are based on a vicious cycle: during mitochondrial dysfunction, the mitochondrial membrane potential reduced, thus decreasing ATP and increasing ROS levels; thereafter, further mitochondrial dysfunction is induced, with the mitochondrial membrane potential reduced, with a concomitant reduction in ATP generation. This vicious cycle causes electrophysiological alterations, thereby causing arrhythmia [150,153]. Proper mitophagy can eliminate damaged mitochondria, maintain mitochondrial homeostasis in cells, and prevent damage to hazardous substances, thus further disrupting cellular phenomena.…”

Section: Arrhythmiamentioning

confidence: 99%

Role of Mitophagy in Cardiovascular Disease

Yang¹,

Li²,

Li³

et al. 2020

Aging and disease

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Cardiovascular disease is the leading cause of mortality worldwide, and mitochondrial dysfunction is the primary contributor to these disorders. Recent studies have elaborated on selective autophagy-mitophagy, which eliminates damaged and dysfunctional mitochondria, stabilizes mitochondrial structure and function, and maintains cell survival and growth. Numerous recent studies have reported that mitophagy plays an important role in the pathogenesis of various cardiovascular diseases. This review summarizes the mechanisms underlying mitophagy and advancements in studies on the role of mitophagy in cardiovascular disease.

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“…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).…”

Section: Role Of Mitochondrial Ca2+ In Metabolism-contraction Coupmentioning

confidence: 99%

New Insights in Cardiac Calcium Handling and Excitation-Contraction Coupling

Gambardella

Trimarco

Iaccarino

et al. 2017

Advances in Experimental Medicine and Biology

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Excitation-contraction (EC) coupling denotes the conversion of electric stimulus in mechanic output in contractile cells. Several studies have demonstrated that calcium (Ca2+) plays a pivotal role in this process. Here we present a comprehensive and updated description of the main systems involved in cardiac Ca2+ handling that ensure a functional EC coupling and their pathological alterations, mainly related to heart failure.

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Functional Role of Mitochondria in Arrhythmogenesis

Cited by 49 publications

References 61 publications

Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms

Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms

Role of Mitophagy in Cardiovascular Disease

New Insights in Cardiac Calcium Handling and Excitation-Contraction Coupling

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