Mitochondrial network energetics in the heart

Aon, Miguel A.; Cortassa, Sonia

doi:10.1002/wsbm.1188

Cited by 27 publications

(21 citation statements)

References 117 publications

(315 reference statements)

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“…Rather, they appear to be highly mobile entities forming dynamic networks of long tubules. The functional and morphological behavior of mitochondrial networks largely influences the bioenergetic status of cells, tissues, and organs (11) and confers properties typical of complex systems, such as robustness, redundancy of function, and plasticity (6). These properties provide the system with the adaptive flexibility needed to adjust to changing stresses and metabolic demands (6).…”

Section: Role Of Mitochondrial Dynamics In Cardiovascular Phys-mentioning

confidence: 99%

Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics

Marzetti

Csiszár

Dutta

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

175

131

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Advanced age is associated with a disproportionate prevalence of cardiovascular disease (CVD). Intrinsic alterations in the heart and the vasculature occurring over the life course render the cardiovascular system more vulnerable to various stressors in late life, ultimately favoring the development of CVD. Several lines of evidence indicate mitochondrial dysfunction as a major contributor to cardiovascular senescence. Besides being less bioenergetically efficient, damaged mitochondria also produce increased amounts of reactive oxygen species, with detrimental structural and functional consequences for the cardiovascular system. The agerelated accumulation of dysfunctional mitochondrial likely results from the combination of impaired clearance of damaged organelles by autophagy and inadequate replenishment of the cellular mitochondrial pool by mitochondriogenesis. In this review, we summarize the current knowledge about relevant mechanisms and consequences of age-related mitochondrial decay and alterations in mitochondrial quality control in the cardiovascular system. The involvement of mitochondrial dysfunction in the pathogenesis of cardiovascular conditions especially prevalent in late life and the emerging connections with neurodegeneration are also illustrated. Special emphasis is placed on recent discoveries on the role played by alterations in mitochondrial dynamics (fusion and fission), mitophagy, and their interconnections in the context of age-related CVD and endothelial dysfunction. Finally, we discuss pharmacological interventions targeting mitochondrial dysfunction to delay cardiovascular aging and manage CVD. oxidative stress; mitophagy; fusion and fission; neurodegeneration; resveratrol THIS ARTICLE is part of a collection on Mitochondria in Cardiovascular Physiology and Disease. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.Advanced age is associated with excessive incidence and prevalence of cardiovascular disease (CVD). Over 80% of cases of coronary artery disease (CAD) and more than 75% of those of congestive heart failure (CHF) are observed in elderly patients (113). The incidence of CVD, including CAD, CHF, and stroke, increases from 4 -10/1,000 person-years in adults aged 45-54 years to 65-75/1,000 person-years in those older than 85 (112). CVD is also a major cause of chronic disability in advanced age (140). Indeed, subclinical CVD is associated with a decline in physical and cognitive function equivalent to over 5 years of aging (136). Similarly, neurodegenerative disorders, such as vascular dementia and Alzheimer's disease (AD), pose a major problem to global public health (45,90).Although the long-term exposure to cardiovascular risk factors plays a major role in the etiopathogenesis of CVD and neurodegeneration, intrinsic aging of the heart and the vasculature greatly enhances the susceptibility to developing CVD and neurodegenerative conditions in late life (100). The cardiovascular sy...

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Section: Role Of Mitochondrial Dynamics In Cardiovascular Phys-mentioning

confidence: 99%

Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics

Marzetti

Csiszár

Dutta

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

175

131

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“…The network organization of mitochondrial structure-function can be characterized from at least four different perspectives [13, 40]: (i) architectural (structural morphology, e.g. punctuated, fused), (ii) topological (spatial connectivity, e.g.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial health, the epigenome and healthspan

et al. 2016

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Food nutrients and metabolic supply-demand dynamics constitute environmental factors that interact with our genome influencing health and disease states. These gene–environment interactions converge at the metabolic-epigenome-genome axis to regulate gene expression and phenotypic outcomes. Mounting evidence indicates that nutrients and lifestyle strongly influence genome-metabolic functional interactions determining disease via altered epigenetic regulation. The mitochondrial network is a central player of the metabolic-epigenome-genome axis, regulating the level of key metabolites (NAD+, AcCoA, ATP) acting as substrates/cofactors for acetyl transferases, kinases (e.g., protein kinase A), deacetylases (e.g., sirtuins). The chromatin, an assembly of DNA and nucleoproteins, regulates the transcriptional process, acting at the epigenomic interface between metabolism and the genome. Within this framework, we review existing evidence showing that preservation of mitochondrial network function is directly involved in decreasing the rate of damage accumulation thus slowing aging and improving healthspan.

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“…However, the network's topology (or connectivity properties) as opposed to its architectural organization (see Aon and Cortassa, 2012 for a review) has not yet been investigated quantitatively in terms of its clustering properties. Mitochondria in cardiac myocytes serve as the main energy supplier and modulator of the myocyte's mechanical and electrical processes, but are also modulated by the latter; therefore, the mitochondrial network's topological heterarchy becomes increasingly complex and non-linear (Yates, 1993).…”

Section: Introductionmentioning

confidence: 99%

Cardiac mitochondria exhibit dynamic functional clustering

et al. 2014

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Multi-oscillatory behavior of mitochondrial inner membrane potential ΔΨm in self-organized cardiac mitochondrial networks can be triggered by metabolic or oxidative stress. Spatio-temporal analyses of cardiac mitochondrial networks have shown that mitochondria are heterogeneously organized in synchronously oscillating clusters in which the mean cluster frequency and size are inversely correlated, thus suggesting a modulation of cluster frequency through local inter-mitochondrial coupling. In this study, we propose a method to examine the mitochondrial network's topology through quantification of its dynamic local clustering coefficients. Individual mitochondrial ΔΨm oscillation signals were identified for each cardiac myocyte and cross-correlated with all network mitochondria using previously described methods (Kurz et al., 2010a). Time-varying inter-mitochondrial connectivity, defined for mitochondria in the whole network whose signals are at least 90% correlated at any given time point, allowed considering functional local clustering coefficients. It is shown that mitochondrial clustering in isolated cardiac myocytes changes dynamically and is significantly higher than for random mitochondrial networks that are constructed using the Erdös–Rényi model based on the same sets of vertices. The network's time-averaged clustering coefficient for cardiac myocytes was found to be 0.500 ± 0.051 (N = 9) vs. 0.061 ± 0.020 for random networks, respectively. Our results demonstrate that cardiac mitochondria constitute a network with dynamically connected constituents whose topological organization is prone to clustering. Cluster partitioning in networks of coupled oscillators has been observed in scale-free and chaotic systems and is therefore in good agreement with previous models of cardiac mitochondrial networks.

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Mitochondrial network energetics in the heart

Cited by 27 publications

References 117 publications

Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics

Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics

Mitochondrial health, the epigenome and healthspan

Cardiac mitochondria exhibit dynamic functional clustering

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