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

Pennanen, Christian; Parra, Valentina; López-Crisosto, Camila; Morales, Pablo E.; Campo, Andrea del; Gutiérrez, Tomás; Rivera-Mejías, Pablo; Kuzmicic, Jovan; Chiong, Mario; Zorzano, António; Rothermel, Beverly A.; Lavandero, Sergio

doi:10.1242/jcs.139394

Cited by 139 publications

(162 citation statements)

References 104 publications

(103 reference statements)

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“…A previous work reported that Ca 2+ influx through voltage-dependent Ca 2+ channels induced by high K + led to mitochondrial fission in neurons and Hela cells 22 ; a recent work demonstrated that norepinephrine induced mitochondrial fission in cultured cardiomyocytes, which was attributed to the stimulation of α1-adrenergic receptors and the consequent increase of intracellular [Ca 2+ ] i. 23 These reports were similar to the present finding in smooth muscle cells. We prechelated the cytosolic Ca 2+ with BAPTA-AM in smooth muscle cells and found that the mitochondrial fission and mito-ROS generation induced by high K + was prevented.…”

Section: Discussionsupporting

confidence: 90%

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: Discussionsupporting

confidence: 90%

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction

Jin

et al. 2016

Hypertension

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“…In the endocrine pancreas of mice exposed to a high-fat diet, metabolic changes associated to hypertrophy were found to be more accentuated in males (85). Alterations in processes related to mitochondrial biogenesis also play a role in hypertrophy (90). Interestingly, these processes can be differentially regulated by female and male sex hormones (91).…”

Section: Figmentioning

confidence: 99%

Stable Isotope Labeling with Amino Acids (SILAC)-Based Proteomics of Primary Human Kidney Cells Reveals a Novel Link between Male Sex Hormones and Impaired Energy Metabolism in Diabetic Kidney Disease

Clotet

Soler

Riera

et al. 2017

Molecular & Cellular Proteomics

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Male sex predisposes to many kidney diseases. Considering that androgens exert deleterious effects in a variety of cell types within the kidney, we hypothesized that dihydrotestosterone (DHT) would alter the biology of the renal tubular cell by inducing changes in the proteome. We employed stable isotope labeling with amino acids (SILAC) in an indirect spike-in fashion to accurately quantify the proteome in DHT-and 17␤-estradiol (EST)-treated human proximal tubular epithelial cells (PTEC). Of the 5043 quantified proteins, 76 were differentially regulated. Biological processes related to energy metabolism were significantly enriched among DHT-regulated proteins. SILAC ratios of 3 candidates representing glycolysis, Nacetylglucosamine metabolism and fatty acid ␤-oxidation, namely glucose-6-phosphate isomerase (GPI), glucosamine-6-phosphate-N-acetyltransferase 1 (GNPNAT1), and mitochondrial trifunctional protein subunit alpha (HADHA), were verified in vitro. In vivo, renal GPI and HADHA protein expression was significantly increased in males. Furthermore, male sex was associated with significantly higher GPI, GNPNAT1, and HADHA kidney protein expression in two different murine models of diabetes. Enrichment analysis revealed a link between our DHTregulated proteins and oxidative stress within the diabetic kidney. This finding was validated in vivo, as we observed increased oxidative stress levels in control and diabetic male kidneys, compared with females. This in depth quantitative proteomics study of human primary PTEC response to sex hormone administration suggests that male sex hormone stimulation results in perturbed energy metabolism in kidney cells, and that this perturbation results in increased oxidative stress in the renal cortex. Chronic Kidney Disease (CKD)1 often results in irreversible deterioration of renal function that can progress to renal failure (1). Sex plays a relevant role in the progression and severity of many kidney diseases (2). At a clinical level, it is From the ‡Department

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“…It has been demonstrated that NE promotes mitochondrial fission leading to a decrease in the mitochondrial mean volume and an increase in the relative number of mitochondria per cell in rat neonatal cardiomyocytes (Pennanen et al 2014). However, in contrast to pig pinealocytes, NE acts on cardiomyocytes through alpha 1 -adrenoceptors.…”

Section: Discussionmentioning

confidence: 99%

“…These phenomena are associated with changes in cell metabolism, cell development, and cell death. They are also involved in the transmission of signaling messengers and the exchange of metabolites within the cell (Chada and Hollenbeck 2003, Kuzmicic et al 2011, Pennanen et al 2014. Changes in mitochondrial morphology can consequently affect the functioning of the respiratory chain, the regulation of the mitochondrial permeability transition pore, and the interaction with other organelles (Piquereau et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…The role of adrenergic receptors in mitochondrial biogenesis and function has been the subject of many investigations performed on various cell types (Chiang et al 2012, Wills et al 2012, Branco et al 2013, Peterson et al 2013, Pennanen et al 2014. The aim of the present study was to characterize the effect of NE as well as β-and α 1 -adrenergic agonists on mitochondria in pig pinealocytes in organ culture.…”

Section: Introductionmentioning

confidence: 92%

See 1 more Smart Citation

Adrenergic control of pinealocyte chondriome – an in vitro study

Przybylska‐Gornowicz¹,

Lewczuk²,

Ziółkowska³

et al. 2016

Polish Journal of Veterinary Sciences

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Norepinephrine released from sympathetic innervation plays the main role in the regulation of melatonin secretion in mammalian pinealocytes. The present study was conducted for the following reasons: 1) to establish whether the pinealocyte chondriome is controlled by norepinephrine, 2) to determine the effect of adrenergic stimulation on mitochondria, and 3) to characterize adrenoceptors involved in the regulation of the chondriome.The static organ culture of the pineal gland was used. The explants were incubated for 5 consecutive days in control medium and between 20:00 and 08:00 in medium with the presence of 10 μM norepinephrine -adrenergic agonist; isoproterenol -beta-adrenoceptor agonist; cirazoline, methoxamine, M-6364 -alfa 1 -adrenoceptors agonists or PMA -activator of PKC. The explants were then subjected to ultrastructural examination and morphometric analysis.The incubation of explants in the presence of norepinephrine or isoproterenol caused a decrease in the relative volume and the numerical density of mitochondria and induced an increase in the percentage of free mitochondria in pinealocytes. Significant changes in these parameters were not observed after treatment with methoxamine, cirazoline, M-6463 and PMA.The results obtained show that the chondriome of pig pinealocytes is controlled by norepinephrine acting via beta-adrenoceptors. Adrenergic stimulation, repeated for five consecutive days of organ culture, causes a decrease in the number of mitochondria and a shift in the distribution of mitochondria from the form of networks and filaments into the form of single particles. This indicates the intensive remodeling of the mitochondria network, which is closely linked to the metabolic status of the cell.

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

Cited by 139 publications

References 104 publications

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction

Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction

Stable Isotope Labeling with Amino Acids (SILAC)-Based Proteomics of Primary Human Kidney Cells Reveals a Novel Link between Male Sex Hormones and Impaired Energy Metabolism in Diabetic Kidney Disease

Adrenergic control of pinealocyte chondriome – an in vitro study

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