Polycystin-2-dependent control of cardiomyocyte autophagy

Criollo, Alfredo; Altamirano, Francisco; Pedrozo, Zully; Schiattarella, Gabriele Giacomo; Li, Dan L.; Rivera-Mejías, Pablo; Sotomayor-Flores, Cristian; Parra, Valentina; Villalobos, Elisa; Battiprolu, Pavan K.; Jiang, Nan; May, Herman I.; Morselli, Eugenia; Somlo, Stefan; Smedt, Humbert De; Gillette, Thomas G.; Lavandero, Sergio; Hill, Joseph A.

doi:10.1016/j.yjmcc.2018.03.002

Cited by 35 publications

(32 citation statements)

References 47 publications

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“…Furthermore, the presence of TRPP2 has been proven in knockout mice who died before birth as a result of cardiac malformations (Pennekamp et al., 2002). Recently, a study confirmed that TRPP2 was able to regulate autophagy through Ca 2+ homeostasis in cardiac myocytes (Criollo et al., 2018). However, there are only few studies which looked on the role of these channels in the function of cardiac cells.…”

Section: Expression Of Trp Channels In Cardiac Cellsmentioning

confidence: 95%

TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling

et al. 2019

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Calcium is an important second messenger required not only for the excitation-contraction coupling of the heart but also critical for the activation of cell signaling pathways involved in the adverse cardiac remodeling and consequently for the heart failure. Sustained neurohumoral activation, pressure-overload, or myocardial injury can cause pathologic hypertrophic growth of the heart followed by interstitial fibrosis. The consequent heart’s structural and molecular adaptation might elevate the risk of developing heart failure and malignant arrhythmia. Compelling evidences have demonstrated that Ca 2+ entry through TRP channels might play pivotal roles in cardiac function and pathology. TRP proteins are classified into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPML (mucolipin), and TRPP (polycystin), which are activated by numerous physical and/or chemical stimuli. TRP channels participate to the handling of the intracellular Ca 2+ concentration in cardiac myocytes and are mediators of different cardiovascular alterations. This review provides an overview of the current knowledge of TRP proteins implication in the pathologic process of some frequent cardiac diseases associated with the adverse cardiac remodeling such as cardiac hypertrophy, fibrosis, and conduction alteration.

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Section: Expression Of Trp Channels In Cardiac Cellsmentioning

confidence: 95%

TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling

et al. 2019

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“…Knockdown or knockout of PC2 reduced the autophagic flux, while PC2 overexpression had the opposite effect 29,31 . PC2-induced autophagy in cardiac cells was blunted by intracellular calcium chelation, whereas removal of extracellular calcium had no effect 29 . These findings suggest a model whereby PC2-dependent regulation of autophagy occurs through the regulation of intracellular calcium homeostasis 29,31 (Fig.…”

Section: Discussionmentioning

confidence: 95%

“…It has been suggested that increased [Ca 2+ ] cyt /[Ca 2+ ] ER , at least partly, contributes to the stimulation of autophagy 59 . Recent findings indicate that in cardiomyocytes, PC2 functions to promote autophagy under glucose starvation or mTOR (target of rapamycin) inhibition 29,31 . Knockdown or knockout of PC2 reduced the autophagic flux, while PC2 overexpression had the opposite effect 29,31 .…”

Section: Discussionmentioning

confidence: 99%

“…Recent findings indicate that in cardiomyocytes, PC2 functions to promote autophagy under glucose starvation or mTOR (target of rapamycin) inhibition 29,31 . Knockdown or knockout of PC2 reduced the autophagic flux, while PC2 overexpression had the opposite effect 29,31 . PC2-induced autophagy in cardiac cells was blunted by intracellular calcium chelation, whereas removal of extracellular calcium had no effect 29 .…”

Section: Discussionmentioning

confidence: 99%

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TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells

et al. 2019

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Mutations in the polycystins cause autosomal dominant polycystic kidney disease (ADPKD). Here we show that transmembrane protein 33 (TMEM33) interacts with the ion channel polycystin-2 (PC2) at the endoplasmic reticulum (ER) membrane, enhancing its opening over the whole physiological calcium range in ER liposomes fused to planar bilayers. Consequently, TMEM33 reduces intracellular calcium content in a PC2-dependent manner, impairs lysosomal calcium refilling, causes cathepsins translocation, inhibition of autophagic flux upon ER stress, as well as sensitization to apoptosis. Invalidation of TMEM33 in the mouse exerts a potent protection against renal ER stress. By contrast, TMEM33 does not influence pkd2 -dependent renal cystogenesis in the zebrafish. Together, our results identify a key role for TMEM33 in the regulation of intracellular calcium homeostasis of renal proximal convoluted tubule cells and establish a causal link between TMEM33 and acute kidney injury.

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“…Esse estudo sugere, também, que as alterações observadas em mutantes para Pkd2 sejam secundárias às anormalidades do Ca 2+ intracelular encontradas nesses animais. Um estudo subsequente revelou, ainda, que camundongos Pkd2 +/apresentam e alterações de transiente de Ca 2+ intracelular em resposta à estimulação elétrica e à cafeína(114).O coração é um órgão metabolicamente muito ativo. De fato, 25 a 30% do volume dos cardiomiócitos é constituído por mitocôndrias.…”

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Camundongos deficientes em Pkd1 apresentam disfunção cardíaca associada a reprogramação metabólica e aumento de inflamação e apoptose

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Aos meus pais, Marcos e Cida, pelo amor, incentivo e apoio incondicional. Ao meu marido, Edwin, por ter aceitado e vivido esse sonho comigo, mesmo que lhe fugindo a razão. Agradecimentos À minha irmã Thais e meu cunhado Carlo por terem me acolhido em sua casa quando vim para São Paulo e minha vida era cheia de incertezas. Por terem me transformado na tia Dessa, a melhor versão de mim mesma! Aos meus sobrinhos, que mesmo sem saberem, me consolaram em momentos de dificuldades, deixando minha vida muito mais colorida e alegre! Ao Professor Luiz Fernando Onuchic pelas oportunidades, ensinamentos, conselhos e pelo entusiasmo científico que muito me motivaram nessa jornada. À Prof a Alicia Kowaltovski pela colaboração, por ter feito renascer em mim a paixão pela pesquisa e principalmente pelo exemplo de pesquisadora, minha enorme gratidão e admiração. Ao Prof. Kinulpe Sampaio pelo auxílio na microscopia eletrônica e pelos bons momentos proporcionados em Belo Horizonte. Ao Dr. Maurício Sforça, Dra Silvana Rocco e Dr. Antônio Bloise pelo auxílio nos experimentos e análises de metabolômica. À Dra Ana Maria Gonçalves da Silva pelos ensinamentos em imunohistoquímica, pelo exemplo de excelência e pela amizade. Ao Dr. Amaro Duarte Neto, médico patologista, pela dedicação e pelo auxílio nas análises histológicas. À Prof a Silvana Bordin e Dr. Gilson Murata pela gentileza em ceder diversos anticorpos utilizados neste trabalho.

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Polycystin-2-dependent control of cardiomyocyte autophagy

Cited by 35 publications

References 47 publications

TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling

TRP Channels: Current Perspectives in the Adverse Cardiac Remodeling

TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells

Camundongos deficientes em Pkd1 apresentam disfunção cardíaca associada a reprogramação metabólica e aumento de inflamação e apoptose

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