Mitochondrial Ca2+ Uniporter–Dependent Energetic Dysfunction Drives Hypertrophy in Heart Failure

Hugo Alves-Figueiredo, Christian Silva-Platas, Manuel Estrada, Yuriana Oropeza-Almazán, Martin Ramos-González, Judith Bernal-Ramírez, Eduardo Vázquez-Garza, Armando Tellez, Felipe Salazar-Ramírez, Abraham Méndez-Fernández, José Luis Galaz, Pedro Lobos, Keith Youker, Omar Lozano, Guillermo Torre-Amione, Gerardo García-Rivas

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The role of the mitochondrial calcium uniporter (MCU) in energy dysfunction and hypertrophy in heart failure (HF) remains unknown. In angiotensin II (ANGII)–induced hypertrophic cardiac cells we have shown that hypertrophic cells overexpress MCU and present bioenergetic dysfunction. However, by silencing MCU, cell hypertrophy and mitochondrial dysfunction are prevented by blocking mitochondrial calcium overload, increase mitochondrial reactive oxygen species, and activation of nuclear factor kappa B–dependent hypertrophic and proinflammatory signaling. Moreover, we identified a calcium/calmodulin–independent protein kinase II/cyclic adenosine monophosphate response element–binding protein signaling modulating MCU upregulation by ANGII. Additionally, we found upregulation of MCU in ANGII-induced left ventricular HF in mice, and in the LV of HF patients, which was correlated with pathological remodeling. Following left ventricular assist device implantation, MCU expression decreased, suggesting tissue plasticity to modulate MCU expression.

Original languageEnglish (US)
Pages (from-to)496-518
Number of pages23
JournalJACC: Basic to Translational Science
Issue number4
StatePublished - Apr 2024


  • heart failure
  • mitochondrial calcium overload
  • mitochondrial calcium uniporter
  • mitochondrial dysfunction
  • pathological remodeling
  • reactive oxygen species

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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