Mitochondrial Dynamics In Heart Cells: Very Low Amplitude High Frequency Fluctuations In Adult Cardiomyocytes And Flow Motion In Non-beating Hl-1 Cells

Béraud, Nathalie; Pelloux, Sophie; Usson, Yves; Kuznetsov, Andrey V.; Ronot, Xavier; Tourneur, Yves; Saks, Valdur

doi:10.1016/j.bpj.2008.12.1197

Cited by 24 publications

(45 citation statements)

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“…In the adult cardiac muscle, mitochondria are arranged in a longitudinal fashion, tightly packed between myofibrils, thus preventing the free movement of mitochondria through the cytosol (Vendelin et al, 2005;Beraud et al, 2009). In electron micrographs of normal heart tissue, intermyofibrillar mitochondria are often observed spanning a single sarcomere from Z-band to Z-band, suggesting that mitochondrial dynamics are under strict topological constraints.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial fission is required for cardiomyocyte hypertrophy via a Ca2+-calcineurin signalling pathway

Pennanen

Parra

López-Crisosto

et al. 2014

Journal of Cell Science

139

152

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Cardiomyocyte hypertrophy has been associated with diminished mitochondrial metabolism. Mitochondria are crucial organelles for the production of ATP, and their morphology and function are regulated by the dynamic processes of fusion and fission. The relationship between mitochondrial dynamics and cardiomyocyte hypertrophy is still poorly understood. Here, we show that treatment of cultured neonatal rat cardiomyocytes with the hypertrophic agonist norepinephrine promotes mitochondrial fission (characterized by a decrease in mitochondrial mean volume and an increase in the relative number of mitochondria per cell) and a decrease in mitochondrial function. We demonstrate that norepinephrine acts through a 1 -adrenergic receptors to increase cytoplasmic Ca 2+ , activating calcineurin and promoting migration of the fission protein Drp1 (encoded by Dnml1) to mitochondria. Dominant-negative Drp1 (K38A) not only prevented mitochondrial fission, it also blocked hypertrophic growth of cardiomyocytes in response to norepinephrine. Remarkably, an antisense adenovirus against the fusion protein Mfn2 (AsMfn2) was sufficient to increase mitochondrial fission and stimulate a hypertrophic response without agonist treatment. Collectively, these results demonstrate the importance of mitochondrial dynamics in the development of cardiomyocyte hypertrophy and metabolic remodeling.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial fission is required for cardiomyocyte hypertrophy via a Ca2+-calcineurin signalling pathway

Pennanen

Parra

López-Crisosto

et al. 2014

Journal of Cell Science

139

152

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“…These morphological transitions are greatly influenced by fusion and fission of the mitochondrial membranes and have been referred to as mitochondrial dynamics (29,46). In adult cardiac myocytes, mitochondria do not display significant motility and they are in close contact with each other (10,81). 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).…”

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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

311

352

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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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“…Limited studies with adult cardiomyocytes have been inconclusive and even controversial. Whereas low-amplitude and high-frequency mitochondrial fluctuations have been visualized and quantified in living adult cardiomyocytes, no mitochondrial fusion and fission was detected (9). In isolated adult rat heart challenged by short periods of hypoxia (10) and in cardiomyopathy patients (11), elongated mitochondria ranging from three to seven sarcomeres in length have been visualized, whereas in cardiomyocytes from heart failure patients and rat models, increased amounts of small and fragmented mitochondria were detected (12), indicating the occurrence of mitochondrial fusion and fission or other as-yetunknown type of dynamic regulation.…”

mentioning

confidence: 99%

Kissing and nanotunneling mediate intermitochondrial communication in the heart

Huang

Sun

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

147

140

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Mitochondria in many types of cells are dynamically interconnected through constant fusion and fission, allowing for exchange of mitochondrial contents and repair of damaged mitochondria. However, constrained by the myofibril lattice, the ∼6,000 mitochondria in the adult mammalian cardiomyocyte display little motility, and it is unclear how, if at all, they communicate with each other. By means of target-expressing photoactivatable green fluorescent protein (PAGFP) in the mitochondrial matrix or on the outer mitochondrial membrane, we demonstrated that the local PAGFP signal propagated over the entire population of mitochondria in cardiomyocytes on a time scale of ∼10 h. Two elemental steps of intermitochondrial communications were manifested as either a sudden PAGFP transfer between a pair of adjacent mitochondria (i.e., "kissing") or a dynamic nanotubular tunnel (i.e., "nanotunneling") between nonadjacent mitochondria. The average content transfer index (fractional exchange) was around 0.5; the rate of kissing was 1‰ s −1 per mitochondrial pair, and that of nanotunneling was about 14 times smaller. Electron microscopy revealed extensive intimate contacts between adjacent mitochondria and elongated nanotubular protrusions, providing a structural basis for the kissing and nanotunneling, respectively. We propose that, through kissing and nanotunneling, the otherwise static mitochondria in a cardiomyocyte form one dynamically continuous network to share content and transfer signals.mitochondrial dynamics | nanotubule I n most cells, mitochondria are highly dynamic organelles that constantly undergo shape changes through fusion and fission. This results in a form of communication that allows for the exchange and distribution of soluble and membranous components, including metabolic intermediates, signaling messengers, proteins, lipids, and mitochondrial DNAs, and provides a mechanism for repairing damaged mitochondria and maintaining a healthy mitochondrial population (1-3). Disorders of mitochondrial fusion and fission have been associated with developmental defects, neurodegenerative diseases, and cardiovascular diseases (4-7).In adult mammalian cardiomyocytes, mitochondria occupy ∼40% of the cell volume and are rigidly organized between bundles of myofilaments (interfibrillar mitochondria), under the sarcolemma (subsarcolemmal mitochondria), and around the nucleus (perinuclear mitochondria). This arrangement and the apparent lack of motility, a prerequisite for mitochondrial fusion in other types of cells, raise the question of whether mitochondria in adult cardiomyocyte communicate with each other dynamically. Mitochondrial dynamics in cardiac cell lines or neonatal cardiomyocytes (8) do not provide a direct answer to this question because mitochondria in these cells are not constrained strictly. Limited studies with adult cardiomyocytes have been inconclusive and even controversial. Whereas low-amplitude and high-frequency mitochondrial fluctuations have been visualized and quantified in living adult cardiomyo...

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Mitochondrial Dynamics In Heart Cells: Very Low Amplitude High Frequency Fluctuations In Adult Cardiomyocytes And Flow Motion In Non-beating Hl-1 Cells

Cited by 24 publications

References 0 publications

Mitochondrial fission is required for cardiomyocyte hypertrophy via a Ca2+-calcineurin signalling pathway

Mitochondrial fission is required for cardiomyocyte hypertrophy via a Ca2+-calcineurin signalling pathway

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

Kissing and nanotunneling mediate intermitochondrial communication in the heart

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