Adrenergic regulation of Drp1-driven mitochondrial fission in cardiac physio-pathology

Bong Sook Jhun, Jin O-Uchi, Stephanie M. Adaniya, Michael W. Cypress, Yisang Yoon

Research output: Contribution to journalReview article

11 Scopus citations

Abstract

Abnormalmitochondrialmorphology, especially fragmentedmitochondria, andmitochondrial dysfunction are hallmarks of a variety of human diseases including heart failure (HF). Although emerging evidence suggests a link between mitochondrial fragmentation and cardiac dysfunction, it is still not well described which cardiac signaling pathway regulates mitochondrial morphology and function under pathophysiological conditions such as HF. Mitochondria change their shape and location via the activity of mitochondrial fission and fusion proteins. This mechanism is suggested as an important modulator for mitochondrial and cellular functions including bioenergetics, reactive oxygen species (ROS) generation, spatiotemporal dynamics of Ca2+ signaling, cell growth, and death in the mammalian cell- and tissue-specific manners. Recent reports show that a mitochondrial fission protein, dynamin-like/related protein 1 (DLP1/Drp1), is post-translationally modified via cell signaling pathways, which control its subcellular localization, stability, and activity in cardiomyocytes/heart. In this review, we summarize the possible molecular mechanisms for causing post-translational modifications (PTMs) of DLP1/Drp1 in cardiomyocytes, and further discuss how these PTMs of DLP1/Drp1 mediate abnormal mitochondrial morphology and mitochondrial dysfunction under adrenergic signaling activation that contributes to the development and progression of HF.

Original languageEnglish (US)
Article number195
JournalAntioxidants
Volume7
Issue number12
DOIs
StatePublished - Dec 2018

Keywords

  • Adrenoceptor
  • Apoptosis
  • Ca/calmodulin-dependent protein kinase II (CAMKII)
  • Calcineurin
  • Gtpase
  • Mitochondrial permeability transition pore
  • Phosphorylation
  • Protein kinase D (PKD)
  • Protein kinase a (PKA)

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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