Interactions between sarco-endoplasmic reticulum and mitochondria in cardiac and skeletal muscle – pivotal roles in Ca2+ and reactive oxygen species signaling

Eisner, Verónica; Csordás, György; Hajnóczky, György

doi:10.1242/jcs.093609

Cited by 185 publications

(179 citation statements)

References 172 publications

(189 reference statements)

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“…29,30 For instance, in cardiomyocytes, mitochondria-derived ROS have been implicated in the modulation of RyR 2 (ryanodine receptor 2)-mediated Ca 2+ -induced Ca 2+ release, thus the regulation of cardiac contraction 31 ; in pulmonary arterial smooth muscle cells, mito-ROS trigger calcium increases, which induces pulmonary vasoconstriction during hypoxia. 32 However, to our knowledge, the regulation of mito-ROS on [Ca 2+ ] i and contractility in systemic vascular smooth muscle cells are not completely understood.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction

Jin

et al. 2016

Hypertension

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H ypertension is one of the most common worldwide diseases and is a major risk factor for a variety of cardiovascular and renal events, including myocardial infarction, stroke, heart failure, and end-stage renal disease. 1 The latest survey shows that hypertension accounts for 7% of global disability adjusted life years and 9.4 million deaths in 2010.2 Therefore, the molecular mechanisms underlying hypertension and the antihypertensive therapies have always been the topics in cardiovascular fields.Mitochondria are dynamic organelles and change their morphology through fission and fusion processes named as mitochondrial dynamics.3 Defects in mitochondrial dynamics are implicated in multiple cardiovascular diseases, for instance, the increased mitochondrial fission contributes to the impairment of endothelial function in diabetes mellitus and the hyperproliferation of pulmonary artery smooth muscle cells in pulmonary arterial hypertension. 4,5 More interestingly, Hong et al 6 show that mitochondrial fission is crucial for O 2 -induced ductus arteriosus constriction and closure at birth in human and rabbits. By using novel digital image processing/single particle tracking techniques, Giedt et al 7 show that mitochondria in endothelial cells continuously undergo fusion/fission, indicating that the onset of biological function related to mitochondrial dynamics should be prompt without needing the transcription and translation processes of mitochondrial dynamic-related proteins. Therefore, we speculate that interfering mitochondrial dynamics could show acute effects on the vascular function. In the present work, we investigate the effects of acute inhibition of mitochondrial fission on the constriction and relaxation of arteries and the underlying mechanisms. We find for the first time that mitochondrial fission of smooth muscle cells is involved in artery constriction, revealing a novel mechanism for vasoconstriction and providing a potential therapeutic target for hypertension. Abstract-Mitochondria

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Section: Discussionmentioning

confidence: 99%

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction

Jin

et al. 2016

Hypertension

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“…In these cells, Eisner et al proposed that the two mitochondrial membranes are in real contact, forming an arrangement of the jSR-OMM-IMM that, ultimately, provide a 'highway' for Ca 2+ delivery from the SR to the mitochondrial matrix. 90 Hence, similar to the distance between the ER and the OMM, the distance between the OMM and the IMM might also be a regulated structural parameter, a possibility that, in turn, would support the existence of a molecular mechanism that organizes the spatial 'sandwich-like' arrangement and, perhaps, the joint tethering, of the ER, OMM and IMM at the sites of Ca 2+ transfer. Such three-membrane structure could regulate the activity of lipid-MERCs because, like MCU, enzymes involved in MERC-mediated lipid biosynthesis are in the IMM.…”

Section: 80mentioning

confidence: 99%

The coming of age of the mitochondria–ER contact: a matter of thickness

2016

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The sites of near-contact between the mitochondrion and the endoplasmic reticulum (ER) have earned a lot of attention due to their key role in the maintenance of lipid and calcium (Ca 2+ ) homeostasis, in the initiation of autophagy and mitochondrial division, and in sensing metabolic shifts. At these sites, typically called MAMs (mitochondria-associated ER membranes) or MERCs (mitochondria-ER contacts), the organelles juxtapose at a distance that can range from~10 to~50 nm. The multifunctional role of this subcellular compartment is puzzling; further, recent studies have shown that mitochondria-ER contacts are highly plastic structures that remodel upon metabolic transitions and that their activity in controlling lipid homeostasis could be involved in Alzheimer's disease pathogenesis. This review aims at integrating the functions of this subcellular compartment to its most characterizing and unexplored structural parameter, their 'thickness': that is, the width of the cleft that separates the cytosolic face of the outer mitochondrial membrane from that of the ER. We describe and discuss the reasons why the thickness of a MERC should be considered a regulated structural parameter of the cell that defines and controls its function. Further, we propose a MERC classification that will help organize the expanding field of MERCs biology and of their role in cell physiology and human disease.

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“…The other role is to control mitochondrial dynamics via fission by targeting of Drp1 (15,16) and via motility by targeting of Miro proteins (17)(18)(19) in the cytoplasm. In some striated muscles, including mammalian myocardium, mitochondria are strategically located for uptake and sensing of small amount of Ca 2+ during its release from the adjoining SR (6,20,21). This makes mitochondria particularly responsive to changes in Ca 2+ homeostasis.…”

Section: Camentioning

confidence: 99%

Increased mitochondrial nanotunneling activity, induced by calcium imbalance, affects intermitochondrial matrix exchanges

Lavorato

Iyer

et al. 2017

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

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Exchanges of matrix contents are essential to the maintenance of mitochondria. Cardiac mitochondrial exchange matrix content in two ways: by direct contact with neighboring mitochondria and over longer distances. The latter mode is supported by thin tubular protrusions, called nanotunnels, that contact other mitochondria at relatively long distances. Here, we report that cardiac myocytes of heterozygous mice carrying a catecholaminergic polymorphic ventricular tachycardia-linked RyR2 mutation (A4860G) show a unique and unusual mitochondrial response: a significantly increased frequency of nanotunnel extensions. The mutation induces Ca 2+ imbalance by depressing RyR2 channel activity during excitation-contraction coupling, resulting in random bursts of Ca 2+ release probably due to Ca 2+ overload in the sarcoplasmic reticulum. We took advantage of the increased nanotunnel frequency in RyR2 A4860G+/− cardiomyocytes to investigate and accurately define the ultrastructure of these mitochondrial extensions and to reconstruct the overall 3D distribution of nanotunnels using electron tomography. Additionally, to define the effects of communication via nanotunnels, we evaluated the intermitochondrial exchanges of matrix-targeted soluble fluorescent proteins, mtDsRed and photoactivable mtPA-GFP, in isolated cardiomyocytes by confocal microscopy. A direct comparison between exchanges occurring at short and long distances directly demonstrates that communication via nanotunnels is slower. mitochondria | nanotunnels | CPVT | RyR2 | mitochondrial dynamics

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Interactions between sarco-endoplasmic reticulum and mitochondria in cardiac and skeletal muscle – pivotal roles in Ca2+ and reactive oxygen species signaling

Cited by 185 publications

References 172 publications

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction

The coming of age of the mitochondria–ER contact: a matter of thickness

Increased mitochondrial nanotunneling activity, induced by calcium imbalance, affects intermitochondrial matrix exchanges

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