Power Grid Protection of the Muscle Mitochondrial Reticulum

Glancy, Brian; Hartnell, Lisa M.; Combs, Christian A.; Femnou, Armel N.; Sun, Junhui; Murphy, Elizabeth; Subramaniam, Sriram; Balaban, Robert S.

doi:10.1016/j.celrep.2017.03.063

Cited by 154 publications

(177 citation statements)

References 32 publications

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“…B), as well as membranous bridges (Fig. C), all supporting the notion of long‐distance communication inside the mitochondrial network (Glancy et al, ).…”

Section: Resultssupporting

confidence: 80%

Mitochondrial Deformation During the Cardiac Mechanical Cycle

Rog-Zielinska

O’Toole

Hoenger

et al. 2018

The Anatomical Record

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Cardiomyocytes both cause and experience continual cyclic deformation. The exact effects of this deformation on the properties of intracellular organelles are not well characterized, although they are likely to be relevant for cardiomyocyte responses to active and passive changes in their mechanical environment. In the present study we provide three‐dimensional ultrastructural evidence for mechanically induced mitochondrial deformation in rabbit ventricular cardiomyocytes over a range of sarcomere lengths representing myocardial tissue stretch, an unloaded “slack” state, and contracture. We also show structural indications for interaction of mitochondria with one another, as well as with other intracellular elements such as microtubules, sarcoplasmic reticulum and T‐tubules. The data presented here help to contextualize recent reports on the mechanosensitivity and cell‐wide connectivity of the mitochondrial network and provide a structural framework that may aide interpretation of mechanically‐regulated molecular signaling in cardiac cells. Anat Rec, 302:146–152, 2019. © 2018 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

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“…B), as well as membranous bridges (Fig. C), all supporting the notion of long‐distance communication inside the mitochondrial network (Glancy et al, ).…”

Section: Resultssupporting

confidence: 80%

Mitochondrial Deformation During the Cardiac Mechanical Cycle

Rog-Zielinska

O’Toole

Hoenger

et al. 2018

The Anatomical Record

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“…), connectivity (Glancy et al . , 2018; Bleck et al . ) and interactions with other organelles (Benador et al .…”

Section: Discussionmentioning

confidence: 99%

“…The discrepancy between our in vivo findings and studies using isolated mitochondria could be explained, in part, by the connectivity of mitochondrial networks (Glancy et al . , ; Bleck et al . ).…”

Section: Discussionmentioning

confidence: 99%

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MitoRACE: evaluating mitochondrial function in vivo and in single cells with subcellular resolution using multiphoton NADH autofluorescence

Willingham

Zhang

Andreoni³

et al. 2019

The Journal of Physiology

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Key points We developed a novel metabolic imaging approach that provides direct measures of the rate of mitochondrial energy conversion with single‐cell and subcellular resolution by evaluating NADH autofluorescence kinetics during the mitochondrial redox after cyanide experiment (mitoRACE). Measures of mitochondrial NADH flux by mitoRACE are sensitive to physiological and pharmacological perturbations in vivo. Metabolic imaging with mitoRACE provides a highly adaptable platform for evaluating mitochondrial function in vivo and in single cells with potential for broad applications in the study of energy metabolism. Abstract Mitochondria play a critical role in numerous cell types and diseases, and structure and function of mitochondria can vary greatly among cells or within different regions of the same cell. However, there are currently limited methodologies that provide direct assessments of mitochondrial function in vivo, and contemporary measures of mitochondrial energy conversion lack the spatial resolution necessary to address cellular and subcellular heterogeneity. Here, we describe a novel metabolic imaging approach that provides direct measures of mitochondrial energy conversion with single‐cell and subcellular resolution by evaluating NADH autofluorescence kinetics during the mitochondrial redox after cyanide experiment (mitoRACE). MitoRACE measures the rate of NADH flux through the steady‐state mitochondrial NADH pool by rapidly inhibiting mitochondrial energetic flux, resulting in an immediate, linear increase in NADH fluorescence proportional to the steady‐state NADH flux rate, thereby providing a direct measure of mitochondrial NADH flux. The experiments presented here demonstrate the sensitivity of this technique to detect physiological and pharmacological changes in mitochondrial flux within tissues of living animals and reveal the unique capability of this technique to evaluate mitochondrial function with single‐cell and subcellular resolution in different cell types in vivo and in cell culture. Furthermore, we highlight the potential applications of mitoRACE by showing that within single neurons, mitochondria in neurites have higher energetic flux rates than mitochondria in the cell body. Metabolic imaging with mitoRACE provides a highly adaptable platform for evaluating mitochondrial function in vivo and in single cells, with potential for broad applications in the study of energy metabolism.

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“…Adult cardiomyocytes have a regionally interconnected mitochondrial subnetwork that is thought to limit the cellular consequences of mitochondrial dysfunction by disconnecting damaged mitochondria within seconds, essentially serving as a local power grid protection . It is conceivable that mitochondrial fragmentation (and the consequent lowering of mitochondrial membrane potential) may protect the remaining mitochondria from the damage of energy overload or ROS .…”

Section: Mitochondrial Structure and Function In The Diabetic Heartmentioning

confidence: 99%

Altered mitochondrial metabolism in the insulin‐resistant heart

et al. 2019

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Obesity‐induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from FA‐induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.

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Power Grid Protection of the Muscle Mitochondrial Reticulum

Cited by 154 publications

References 32 publications

Mitochondrial Deformation During the Cardiac Mechanical Cycle

Mitochondrial Deformation During the Cardiac Mechanical Cycle

MitoRACE: evaluating mitochondrial function in vivo and in single cells with subcellular resolution using multiphoton NADH autofluorescence

Altered mitochondrial metabolism in the insulin‐resistant heart

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