Coordinated Behavior of Mitochondria in Both Space and Time: A Reactive Oxygen Species-Activated Wave of Mitochondrial Depolarization

Brady, Nathan R.; Elmore, Steven P.; Beek, Johannes J.H.G.M. van; Krab, Klaas; Courtoy, Pierre J.; Hue, Louis; Westerhoff, Hans V.

doi:10.1529/biophysj.103.035097

Cited by 109 publications

(120 citation statements)

References 44 publications

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“…3B). Similarly, cellwide oscillations in ATP levels can be triggered by localized ROS production in isolated cardiac myocytes (14,66,67). These oscillations have been attributed to ROS-induced ROS release triggering synchronous cell-wide mitochondrial depolarization by opening of ROS-sensitive inner membrane anion channels (IMACs) (68).…”

Section: Perspective 3: Dynamics Of Cardiovascular Metabolismmentioning

confidence: 99%

Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Network perspectives of cardiovascular metabolism

Weiss

Yang

2006

Journal of Lipid Research

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In this review, we examine cardiovascular metabolism from three different, but highly complementary, perspectives. First, from the abstract perspective of a metabolite network, composed of nodes and links. We present fundamental concepts in network theory, including emergence, to illustrate how nature has designed metabolism with a hierarchal modular scale-free topology to provide a robust system of energy delivery. Second, from the physical perspective of a modular spatially compartmentalized network. We review evidence that cardiovascular metabolism is functionally compartmentalized, such that oxidative phosphorylation, glycolysis, and glycogenolysis preferentially channel ATP to ATPases in different cellular compartments, using creatine kinase and adenylate kinase to maximize efficient energy delivery. Third, from the dynamics perspective, as a network of dynamically interactive metabolic modules capable of self-oscillation. Whereas normally, cardiac metabolism exists in a regime in which excitation-metabolism coupling closely matches energy supply and demand, we describe how under stressful conditions, the network can be pushed into a qualitatively new dynamic regime, manifested as cell-wide oscillations in ATP levels, in which the coordination between energy supply and demand is lost. We speculate how this state of "metabolic fibrillation" leads to cell death if not corrected and discuss the implications for cardioprotection.-Weiss, J. N., L. Yang, and Z. Qu. Network perspectives of cardiovascular metabolism. J. Lipid Res. 2006Res. . 47: 2355Res. -2366. Supplementary key words mitochondriaMuscle cells must adapt rapidly to a much wider range of energy demands than most noncontractile cells. For example, the rate of respiration by cardiac muscle increases by a factor of 15-20 between unloaded and maximal workload conditions (1). This requires a very robust metabolic network that can deliver smooth performance over a wide range of parameters. Although we do not yet fully understand how this is accomplished, new systems biology approaches, complemented by network theory and computer modeling studies, are at the threshold of providing new insights.Cardiovascular metabolism can be viewed as a network of interlinked energy-produced pathways (e.g., oxidative phosphorylation, glycolysis, and glycogenolysis), energyconsuming pathways [e.g., myofilament, sarcoplasmic reticulum (SR), and sarcolemma (SL) ATPases], and energydistributing pathways [e.g., creatine kinase (CK) and adenylate kinase (AK)] (Fig. 1A). In this review, we begin by considering metabolism from a highly abstract perspective, as a metabolite network in which substrates/products are represented as nodes and metabolic enzymes are represented as the links between nodes. We present some fundamental concepts in network theory, including the concept of emergence, and discuss how through Darwinian evolution metabolic networks are likely to have evolved a scale-free hierarchal modular topology that ensures the robustness of this most fundamental ...

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Section: Perspective 3: Dynamics Of Cardiovascular Metabolismmentioning

confidence: 99%

Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Network perspectives of cardiovascular metabolism

Weiss

Yang

2006

Journal of Lipid Research

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“…Oxidative insult potentiates the amount of ROS by stimulating mitochondrial ROS production (ROS-induced ROS release; refs. 28,29), and ROS are able to trigger the opening of the mitochondrial permeability transition pore (28,29) to an extent that collapses the mitochondrial membrane potential and leads to ATP depletion.…”

Section: Introductionmentioning

confidence: 99%

Suppression of KATP channel activity protects murine pancreatic β cells against oxidative stress

et al. 2009

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The enhanced oxidative stress associated with type 2 diabetes mellitus contributes to disease pathogenesis. We previously identified plasma membrane-associated ATP-sensitive K + (K ATP ) channels of pancreatic β cells as targets for oxidants. Here, we examined the effects of genetic and pharmacologic ablation of K ATP channels on loss of mouse β cell function and viability following oxidative stress. Using mice lacking the sulfonylurea receptor type 1 (Sur1) subunit of K ATP channels, we found that, compared with insulin secretion by WT islets, insulin secretion by Sur1 -/-islets was less susceptible to oxidative stress induced by the oxidant H 2 O 2 . This was likely, at least in part, a result of the reduced ability of H 2 O 2 to hyperpolarize plasma membrane potential and reduce cytosolic free Ca 2+ concentration ([Ca 2+ ] c ) in the Sur1 -/-β cells. Remarkably, Sur1 -/-β cells were less prone to apoptosis induced by H 2 O 2 or an NO donor than WT β cells, despite an enhanced basal rate of apoptosis. This protective effect was attributed to upregulation of the antioxidant enzymes SOD, glutathione peroxidase, and catalase. Upregulation of antioxidant enzymes and reduced sensitivity of Sur1 -/-cells to H 2 O 2 -induced apoptosis were mimicked by treatment with the sulfonylureas tolbutamide and gliclazide. Enzyme upregulation and protection against oxidant-induced apoptosis were abrogated by agents lowering [Ca 2+ ] c . Sur1 -/-mice were less susceptible than WT mice to streptozotocin-induced β cell destruction and subsequent hyperglycemia and death, which suggests that loss of K ATP channel activity may protect against streptozotocin-induced diabetes in vivo.

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“…Their morphological variability is confined and depends upon the myocyte compartment that they occupy (e.g., interfibrillar versus subsarcolemmal mitochondria [IFM and SSM, respectively]) (2,53,76). Furthermore, it has been recognized that cardiac mitochondria are arranged in a highly organized pattern and under localized stress conditions can coordinate their membrane potential and propagate depolarizing events throughout the cell, suggesting the existence of interorganellar communication mechanisms (4,14,15,85). Therefore, questions remain as to what are the unique features of mitochondrial dynamics in fully differentiated cardiac myocytes and what is their impact on mitochondrial structure and energetics.…”

mentioning

confidence: 99%

Mitofusin-2 Maintains Mitochondrial Structure and Contributes to Stress-Induced Permeability Transition in Cardiac Myocytes

Papanicolaou

Khairallah

Ngoh

et al. 2011

Molecular and Cellular Biology

313

345

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Mitofusin-2 (Mfn-2) is a dynamin-like protein that is involved in the rearrangement of the outer mitochondrial membrane. Research using various experimental systems has shown that Mfn-2 is a mediator of mitochondrial fusion, an evolutionarily conserved process responsible for the surveillance of mitochondrial homeostasis. Here, we find that cardiac myocyte mitochondria lacking Mfn-2 are pleiomorphic and have the propensity to become enlarged. Consistent with an underlying mild mitochondrial dysfunction, Mfn-2-deficient mice display modest cardiac hypertrophy accompanied by slight functional deterioration. The absence of Mfn-2 is associated with a marked delay in mitochondrial permeability transition downstream of Ca 2؉ stimulation or due to local generation of reactive oxygen species (ROS). Consequently, Mfn-2-deficient adult cardiomyocytes are protected from a number of cell death-inducing stimuli and Mfn-2 knockout hearts display better recovery following reperfusion injury. We conclude that in cardiac myocytes, Mfn-2 controls mitochondrial morphogenesis and serves to predispose cells to mitochondrial permeability transition and to trigger cell death.

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Coordinated Behavior of Mitochondria in Both Space and Time: A Reactive Oxygen Species-Activated Wave of Mitochondrial Depolarization

Cited by 109 publications

References 44 publications

Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Network perspectives of cardiovascular metabolism

Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Network perspectives of cardiovascular metabolism

Suppression of KATP channel activity protects murine pancreatic β cells against oxidative stress

Mitofusin-2 Maintains Mitochondrial Structure and Contributes to Stress-Induced Permeability Transition in Cardiac Myocytes

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